38 results on '"Surfactant protein B"'
Search Results
2. Immature Surfactant Protein B Increases in the Serum of Patients with Calcific Severe Aortic Stenosis.
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Eligini, Sonia, Savini, Carlo, Ghilardi, Stefania, Mallia, Alice, Vieceli Dalla Sega, Francesco, Fortini, Francesca, Mikus, Elisa, Munno, Marco, Modafferi, Gloria, Agostoni, Piergiuseppe, Tremoli, Elena, and Banfi, Cristina
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AORTIC valve ,AORTIC stenosis ,INFLAMMATORY mediators ,HEART valve diseases ,BIOPROSTHETIC heart valves ,AORTIC valve transplantation ,CARDIAC patients - Abstract
Valvular disease is a complex pathological condition that impacts countless individuals around the globe. Due to limited treatments, it is crucial to understand its mechanisms to identify new targets. Valve disease may result in pulmonary venous hypertension, which is linked to compromised functioning of the alveolar and capillary membranes and hindered gas exchange. Nonetheless, the correlation between surfactant proteins (SPs) and valve disease remains unexplored. A total of 44 patients were enrolled in this study, with 36 undergoing aortic valve replacement and 8 needing a second aortic valve substitution due to bioprosthetic valve degeneration. Ten healthy subjects were also included. The results showed that patients who underwent both the first valve replacement and the second surgery had significantly higher levels of immature SP-B (proSP-B) compared to control subjects. The levels of the extra-lung collectin SP-D were higher in patients who needed a second surgery due to bioprosthetic valve degeneration, while SP-A levels remained unchanged. The research also showed that there was no reciprocal relationship between inflammation and SP-D as the levels of inflammatory mediators did not differ between groups. The present study demonstrates that circulating proSP-B serves as a reliable marker of alveolar–capillary membrane damage in patients with valvular heart disease. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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3. Proximal and Distal Bronchioles Contribute to the Pathogenesis of Non-Cystic Fibrosis Bronchiectasis.
- Author
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Takanori Asakura, Kenichi Okuda, Gang Chen, Hong Dang, Takafumi Kato, Yu Mikami, Schworer, Stephen A., Gilmore, Rodney C., Radicioni, Giorgia, Hawkins, Padraig, Barbosa Cardenas, Selene Margarita, Minako Saito, Cawley, Anne Marie, De la Cruz, Gabriela, Chua, Michael, Alexis, Neil E., Yohei Masugi, Noone, Peadar G., Ribeiro, Carla M. P., and Kesimer, Mehmet
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BRONCHIECTASIS ,NUCLEIC acid hybridization ,GENE expression ,BRONCHIOLE diseases ,GENETIC regulation ,IN situ hybridization - Abstract
Rationale: Non-cystic fibrosis bronchiectasis (NCFB) may originate in bronchiolar regions of the lung. Accordingly, there is a need to characterize the morphology and molecular characteristics of NCFB bronchioles. Objectives: Test the hypothesis that NCFB exhibits a major component of bronchiolar disease manifest by mucus plugging and ectasia. Methods: Morphologic criteria and region-specific epithelial gene expression, measured histologically and by RNA in situ hybridization and immunohistochemistry, identified proximal and distal bronchioles in excised NCFB lungs. RNA in situ hybridization and immunohistochemistry assessed bronchiolar mucus accumulation and mucin gene expression. CRISPR-Cas9-mediated IL-1R1 knockout in human bronchial epithelial cultures tested IL-1α and IL-1β contributions to mucin production. Spatial transcriptional profiling characterized NCFB distal bronchiolar gene expression. Measurements and Main Results: Bronchiolar perimeters and lumen areas per section area were increased in proximal, but not distal, bronchioles in NCFB versus control lungs, suggesting proximal bronchiolectasis. In NCFB, mucus plugging was observed in ectatic proximal bronchioles and associated nonectatic distal bronchioles in sections with disease. MUC5AC and MUC5B mucins were upregulated in NCFB proximal bronchioles, whereas MUC5B was selectively upregulated in distal bronchioles. Bronchiolar mucus plugs were populated by IL-1β-expressing macrophages. NCFB sterile sputum supernatants induced human bronchial epithelial MUC5B and MUC5AC expression that was >80% blocked by IL-1R1 ablation. Spatial transcriptional profiling identified upregulation of genes associated with secretory cells, hypoxia, interleukin pathways, and IL-1β-producing macrophages in mucus plugs and downregulation of epithelial ciliogenesis genes. Conclusions: NCFB exhibits distinctive proximal and distal bronchiolar disease. Both bronchiolar regions exhibit bronchiolar secretory cell features and mucus plugging but differ in mucin gene regulation and ectasia. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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4. 不 同 浓 度 PM2.5 对 小 鼠 肺 泡 II 型 上 皮 细 胞 MLE-12 的损伤作用及SP-B表达影响.
- Author
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李本, 彭倩, 高永峰, 肖瑶, 陈纪涛, and 刘季芳
- Abstract
Copyright of Shandong Medical Journal is the property of Shandong Medical Health Newspapers and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2023
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5. Surfactant Protein B Plasma Levels: Reliability as a Biomarker in COPD Patients.
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D'Ascanio, Michela, Viccaro, Fausta, Pizzirusso, Dario, Guerrieri, Giulio, Pagliuca, Alessandra, Guerrini, Simone, Innammorato, Marta, De Vitis, Claudia, Raffa, Salvatore, Pezzuto, Aldo, and Ricci, Alberto
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BLOOD proteins ,CHRONIC obstructive pulmonary disease ,SURFACE active agents ,ENZYME-linked immunosorbent assay ,BIOMARKERS - Abstract
Background: The diagnosis of COPD is based on both clinical signs and functional tests. Although there are different functional tests used to assess COPD, no reliable biomarkers able to provide information on pathogenesis and severity are available. The aim of the present study is to explore the relationship between surfactant protein B (Sp-B) serum levels and clinical, radiological, and functional pulmonary parameters in COPD patients. Methods: Forty COPD patients and twenty smokers without airflow limitations or respiratory symptoms were enrolled. Each patient was given questionnaires (CAT and mMRC) and 6MWT, spirometry, DLCO, and computer tomography (CT) were performed. All participants underwent a venous blood sample drawing, and quantitative detection of their Sp-B plasma levels was performed by an enzyme-linked immunosorbent assay. The spirometry and Sp-B plasma levels were assessed after 12 months. Results: A statistically significant difference was found in the plasma Sp-B levels between COPD patients compared to the other group (4.72 + 3.2 ng/mL vs. 1.78 + 1.5 ng/mL; p < 0.001). The change in FEV1 after 12 months (Delta FEV1) showed a significantly negative correlation with respect to the change in Sp-B levels (Delta SpB) (r = −0.4; p < 0.05). This correlation indicates that increasing the plasma dosage of SpB is a foretoken of functional decline. Conclusions: SpB may be considered as a useful marker in COPD assessment and provides prognostic information on lung functional decline. Despite its usefulness, further studies are needed to define its reliability as a biomarker. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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6. Structural and functional stability of the sulfur-free surfactant protein B peptide mimic B-YL in synthetic surfactant lipids.
- Author
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Walther, Frans J., Sharma, Shantanu, Gordon, Larry M., and Waring, Alan J.
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STRUCTURAL stability ,SURFACE active agents ,RESPIRATORY distress syndrome ,LEUCINE ,LIPIDS ,PREMATURE infants - Abstract
Background: Optimal functionality of synthetic lung surfactant for treatment of respiratory distress syndrome in preterm infants largely depends on the quality and quantity of the surfactant protein B (SP-B) peptide mimic and the lipid mixture. B-YL peptide is a 41-residue sulfur-free SP-B mimic with its cysteine and methionine residues replaced by tyrosine and leucine, respectively, to enhance its oxidation resistance.Aim: Testing the structural and functional stability of the B-YL peptide in synthetic surfactant lipids after long-term storage.Methods: The structural and functional properties of B-YL peptide in surfactant lipids were studied using three production runs of B-YL peptides in synthetic surfactant lipids. Each run was held at 5 °C ambient temperature for three years and analyzed with structural and computational techniques, i.e., MALDI-TOF mass spectrometry, ATR-Fourier Transform Infrared Spectroscopy (ATR-FTIR), secondary homology modeling of a preliminary B-YL structure, and tertiary Molecular Dynamic simulations of B-YL in surfactant lipids, and with functional methods, i.e., captive bubble surfactometry (CBS) and retesting in vivo surface activity in surfactant-deficient young adult rabbits.Results: MALDI-TOF mass spectrometry showed no degradation of the B-YL peptide as a function of stored time. ATR-FTIR studies demonstrated that the B-YL peptide still assumed stable alpha-helical conformations in synthetic surfactant lipids. These structural findings correlated with excellent in vitro surface activity during both quasi-static and dynamic cycling on CBS after three years of cold storage and in vivo surface activity of the aged formulations with improvements in oxygenation and dynamic lung compliance approaching those of the positive control surfactant Curosurf®.Conclusions: The structure of the B-YL peptide and the in vitro and in vivo functions of the B-YL surfactant were each maintained after three years of refrigeration storage. [ABSTRACT FROM AUTHOR]- Published
- 2021
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7. 新生小鼠肺泡II型上皮细胞的分离方法.
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国敏, 郝佳琳, 朱庆锋, 李丹妮, and 李小曼
- Abstract
Copyright of Journal of China Medical University is the property of Journal of China Medical University Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2020
- Full Text
- View/download PDF
8. Trafficking of newly synthesized surfactant protein B to the lamellar body in alveolar type II cells.
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Osanai, Kazuhiro, Mizuno, Shiro, Toga, Hirohisa, and Takahashi, Keiji
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SURFACE active agents ,GOLGI apparatus ,CELL fractionation ,PULMONARY surfactant ,CELLS ,PROTEINS - Abstract
Lung surfactant accumulates in the lamellar body (LB) via not only the secretory (anterograde) pathway but also the endocytic (retrograde) pathway. Our previous studies suggested that the major surfactant components, phosphatidylcholine and surfactant protein A take independent trafficking routes in alveolar type II cells. Thus, trafficking of surfactant protein B (SP-B), a major hydrophobic surfactant apoprotein, should be re-evaluated by a straightforward method. Radiolabeling of cells and subsequent cell fractionation were employed to pursue the sequential trafficking of newly synthesized SP-B in rabbit alveolar type II cells. The LB fraction was prepared by gradient ultracentrifugation. Immunoprecipitation from the culture medium, total cells, and LB fraction was carried out with anti-SP-B antibody. Newly synthesized [
35 S]-pro-SP-B (~ 42 kDa) was detected in the cells after 1 h. An ~ 8-kDa mature form of [35 S]-SP-B was detected in the cells after 3 h and in the LB after 6 h. Mature [35 S]-SP-B was predominant in the cells after 24 h, and the dominant portion was present in the LB. In contrast, only a small amount of mature [35 S]-SP-B was present in the culture medium. Molecular processing of ~ 42 kDa [35 S]-pro-SP-B and transport to the LB was inhibited by brefeldin A, which disassembles the Golgi apparatus. These results suggest that newly synthesized SP-B is sorted to the LB via the Golgi and stored until exocytosis. This pathway is distinct from the pathways reported for phosphatidylcholine and surfactant protein A. [ABSTRACT FROM AUTHOR]- Published
- 2020
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9. The reduction in FOXA2 activity during lung development in fetuses from diabetic rat mothers is reversed by Akt inhibition.
- Author
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Zhang, Qingmiao, Chai, Xinqun, Deng, Feitao, Ouyang, Weixiang, and Song, Ting
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LUNG development ,FORKHEAD transcription factors ,PULMONARY surfactant-associated protein B ,PULMONARY surfactant-associated protein C ,DIABETES - Abstract
Hyperglycemia during pregnancy is associated with fetal lung development disorders and surfactant protein (SP) deficiency. Here, we examined the role of FOXA2 and Akt signaling in fetal lung development during diabetic pregnancy. Sprague‐Dawley rats were injected with streptozocin (STZ) during pregnancy to induce diabetes (DM). DM‐exposed fetal lungs exhibited reduced numbers of alveoli, irregularities in the appearance and thickness of the alveolar septum, increased levels of glycogen and lipids in type II alveolar epithelial cells, fewer microvilli and mature lamellar bodies, and swollen mitochondria. SP‐B and SP‐C in DM amniotic fluid and DM lungs were lower than in the control group (P < 0.05). DM lung nuclear FOXA2 was lower compared with the control group (P < 0.05), but p‐FOXA2 was higher (P < 0.05). In murine lung epithelial (MLE) 12 cells, p‐AKT levels were increased by high glucose/insulin, but decreased by the Akt inhibitor MK2206 (P < 0.05). Expression of nuclear FOXA2 was increased by MK2206 compared with the high glucose/insulin group (P < 0.05). These results suggest that maternal diabetes induces fetal lung FOXA2 phosphorylation through the Akt pathway, and also affects the maturation of alveolar epithelial cells and reduces levels of SP‐B and SP‐C in the fetal lungs. An Akt inhibitor reversed the changes in SP expression in vitro. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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10. Surfactant Protein B Suppresses Lung Cancer Progression by Inhibiting Secretory Phospholipase A2 Activity and Arachidonic Acid Production.
- Author
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Lee, Sungmin, Kim, Daehoon, Kang, JiHoon, Kim, EunGi, Kim, Wanyeon, Youn, HyeSook, and Youn, BuHyun
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PULMONARY surfactant-associated protein B ,CANCER treatment ,NON-small-cell lung carcinoma ,ARACHIDONIC acid ,MESENCHYME ,PHOSPHOLIPASE A2 - Abstract
Background/Aims: Radiotherapy is applied to patients with inoperable cancer types including advanced stage non-small cell lung cancer (NSCLC) and radioresistance functions as a critical obstacle in radiotherapy. This study was aimed to investigate the mechanism of radioresistance regulated by surfactant protein B (SP-B). Methods: To investigate the role of SP-B in radioresistance, ΔSFTPB A549 cell line was established and SP-B expression was analyzed. In response to ionizing radiation (IR), the change of SP-B expression was analyzed in A549 and NCI-H441 cell lines. Conditioned media (CM) from NSCLC cells were utilized to evaluate the downstream signaling pathway. The in vivo effects of SP-B were assessed through mouse xenograft model with intratumoral injection of CM. Results: In response to IR, NSCLC cell lines showed decreased SP-B regulated by the TGF-β signaling and decreased SP-B stimulated cell survival and epithelial-mesenchymal transition. Treatment with CM from irradiated cells activated sPLA
2 , enhanced protein kinase Cδ-MAPKs signaling pathway, and increased arachidonic acid production. We confirmed the in vivo roles of SP-B through mouse xenograft model. Conclusion: Our results revealed that down-regulation of SP-B was involved in the radiation-induced metastatic conversion of NSCLC and provided evidence that SP-B acted as a suppressor of NSCLC progression. [ABSTRACT FROM AUTHOR]- Published
- 2017
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11. Diagnostic value of the lung surfactant in sudden infant death syndrome (SIDS).
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Baratovich, Shodiev Gafur, Rakhimovich, Tukhtaev Kadir, and Asomovich, Giyasov Zayniddin
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SUDDEN infant death syndrome ,PULMONARY surfactant ,DIAGNOSTIC errors - Abstract
Morphological, physic-chemical and immunohistochemical properties of the lung surfactant from 50 corpses of infants aged 1 month to 1 year were studied. In the babies with sudden infant death syndrome (SIDS) the physic-chemical studies have shown pronounced decrease of the surfactant stability. Immunohistochemistry revealed decreased expression of surfactant protein B in most cases of SIDS, which is probably due to qualitative changes in lung surfactant. The comprehensive studies of lung surfactant of infants may contribute to clarifying the degree of risk and more accurately determining the causes of death in some cases of sudden infant death. This will help reduce the risk of diagnostic errors, i.e., hypo- or over-diagnosis SIDS and is of practical importance for forensic examination. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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12. Changes in respiratory elastance after deep inspirations reflect surface film functionality in mice with acute lung injury.
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Ayuko Takahashi, Bartolák-Suki, Erzsébet, Majumdar, Arnab, and Suki, Béla
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PULMONARY surfactant ,LUNG injuries ,ANIMAL models in research ,RESPIRATORY organ physiology ,LABORATORY mice ,PHYSIOLOGY - Abstract
Pulmonary surfactant reduces surface tension in the lung and prevents alveolar collapse. Following a deep inspiration (DI), respiratory elastance first drops then gradually increases due to surface film and tissue viscoelasticity. In acute lung injury (ALI), this increase is faster and governed by alveolar collapse due to increased surface tension. We hypothesized that the rate of increase in elastance reflects the deficiency of surfactant in the lung. To test this, mice were ventilated before (baseline) and after saline lavage obtained by injecting 0.8 ml and withdrawing 0.7 ml fluid (severe ALI) or injecting 0.1 ml (mild ALI). After two DIs, elastance was tracked for 10 min followed by a full lavage to assess surfactant proteins B (SP-B) and C (SP-C) content. Following 2 DIs, the increases in elastance during 10 min ventilation (ΔH) were 3.60 ± 0.61, 5.35 ± 1.04, and 8.33 ± 0.84 cmH
2 O/ml in baseline mice and mice with mild and severe ALI, respectively (P < 0.0001). SP-B and SP-C in the lavage fluid dropped by 32.4% and 24.9% in the mild and 50.4% and 39.6% in the severe ALI, respectively. Furthermore, ΔH showed a strong negative correlation with both SP-B (r² = 0.801) and SP-C (r ² = 0.810) content. The ΔH was, however, much smaller when the lavage fluid also contained exogeneous SP-B and SP-C. Thus ΔH can be interpreted as an organ level measure of surface film functionality in lavage-induced ALI in mice. This method could prove useful in clinical situations such as diagnosing surfactant problems, monitoring recovery from lung injury or the effectiveness of surfactant therapy. [ABSTRACT FROM AUTHOR]- Published
- 2015
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13. NOS-2 Inhibition in Phosgene-Induced Acute Lung Injury.
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Filipczak, Piotr T., Senft, Albert P., Seagrave, JeanClare, Weber, Waylon, Kuehl, Philip J., Fredenburgh, Laura E., McDonald, Jacob D., and Baron, Rebecca M.
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NITRIC-oxide synthases ,ENZYME inhibitors ,LUNG injuries ,PHOSGENE ,PULMONARY edema ,OXIDATIVE stress - Abstract
Phosgene exposure via an industrial or warfare release produces severe acute lung injury (ALI) with high mortality, characterized by massive pulmonary edema, disruption of epithelial tight junctions, surfactant dysfunction, and oxidative stress. There are no targeted treatments for phosgene-induced ALI. Previous studies demonstrated that nitric oxide synthase 2 (NOS-2) is upregulated in the lungs after phosgene exposure; however, the role of NOS-2 in the pathogenesis of phosgene-induced ALI remains unknown. We previously demonstrated that NOS-2 expression in lung epithelium exacerbates inhaled endotoxin-induced ALI in mice, mediated partially through downregulation of surfactant protein B (SP-B) expression. Therefore, we hypothesized that a selective NOS-2 inhibitor delivered to the lung epithelium by inhalation would mitigate phosgene-induced ALI. Inhaled phosgene produced increases in bronchoalveolar lavage fluid protein, histologic lung injury, and lung NOS-2 expression at 24 h. Administration of the selective NOS-2 inhibitor 1400W via inhalation, but not via systemic delivery, significantly attenuated phosgene-induced ALI and preserved epithelial barrier integrity. Furthermore, aerosolized 1400Waugmented expression of SP-B and prevented downregulation of tight junction protein zonula occludens 1 (ZO-1), both critical for maintenance of normal lung physiology and barrier integrity. We also demonstrate for the first time that NOS-2-derived nitric oxide downregulates the ZO-1 expression at the transcriptional level in human lung epithelial cells, providing a novel target for ameliorating vascular leak in ALI. Our data demonstrate that lung NOS-2 plays a critical role in the development of phosgene-induced ALI and suggest that aerosolized NOS-2 inhibitors offer a novel therapeutic strategy for its treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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14. Surfactant Proteins A, B, C and D in the Human Nasal Airway: Associated with Mucosal Glands and Ciliated Epithelium but Absent in Fluid-Phase Secretions and Mucus.
- Author
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Gaunsbaek, Maria Q., Kjeldsen, anette D., Svane-Knudsen, Viggo, Henriksen, Maiken L., and Hansen, Soren
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AIRWAY (Anatomy) ,PULMONARY surfactant-associated protein A ,PULMONARY surfactant-associated protein B ,PULMONARY surfactant-associated protein C ,PULMONARY surfactant-associated protein D ,NASAL mucosa ,IMMUNOHISTOCHEMISTRY ,BIOPSY - Abstract
Aims: To investigate the presence of surfactant protein (SP) A, B, C and D in nasal airways and to determine whether the proteins exert their main functions in nasal secretions or in the deeper layers of the nasal mucosa. Methods: Volunteers were recruited from the Department of ENT Head and Neck Surgery, Odense University Hospital, Denmark. The study included 39 subjects. Nasal mucosal biopsies were analyzed by immunohistochemistry, and bronchoalveolar and nasal lavages, nasal brush biopsies and nasal mucus were analyzed for SP-A, -B, -C and -D by SDS-PAGE and Western blotting. The presence of SP-A and SP-D in the first three samplings were also analyzed by enzyme-linked immunosorbent assay. Results: In nasal mucosal biopsies, SP-A, -B, -C and -D were all demonstrated in the serous acini of the submucosal glands and in the surface epithelium. SP-D was detected in nasal brush biopsies, whereas the other SPs were absent. Moreover, SP-A, -B, -C and -D were absent in nasal lavage and mucus. Conclusion: SP-A, -B, -C and -D exert their protective effect in the ductal epithelium of the submucosal glands rather than in nasal secretions and mucus. Further studies are required to clarify the functions of these proteins in nasal secretory pathways for understanding upper airway diseases. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
- Published
- 2015
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15. Production of recombinant forms of the propeptide COOH-terminal and the saposin B-type domain of the propeptide NH2-terminal of the precursor of pulmonary surfactant protein B.
- Author
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Bañares-Hidalgo, A., Cabré, E. J., Gil, F., Bolaños, A., Aller, S., Amor, B., Castañer, G., Herráiz, A., Inaraja, V., Linares, M., Sanz, L., Pérez-Gil, J., and Estrada, P.
- Subjects
PULMONARY surfactant-associated protein B ,SAPOSINS ,PULMONARY surfactant ,PROTEIN expression ,BIOSYNTHESIS - Published
- 2009
16. Expression, purification and characterization of the precursor of human pulmonary surfactant protein B (preproSPB) produced in Escherichia coli.
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Cabré, Elisa J., Gil-Dones, F., and Pérez-Gil, Jesús
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PULMONARY surfactant-associated protein B ,SAPOSINS ,SURFACE tension ,RESPIRATORY distress syndrome ,PULMONARY surfactant - Published
- 2009
17. Association of surfactant protein B gene polymorphisms (C/A-18, C/T1580, intron 4 and A/G9306) and haplotypes with bronchopulmonary dysplasia in chinese han population.
- Author
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Cai, Bao-huan, Chang, Li-wen, Li, Wen-bin, Liu, Wei, Wang, Xi-juan, Mo, Lu-xia, Zhao, Ling-xia, Xu, Hong-tao, and Yang, Hui
- Abstract
This study aimed to investigate the association between surfactant protein B (SP-B) polymorphisms and bronchopulmonary dysplasia (BPD) in Chinese Han infants. We performed a casecontrol study including 86 infants with BPD and 156 matched controls. Genotyping was performed by sequence specific primer-polymerase chain reaction (PCR) and haplotypes were reconstructed by the fastPHASE software. The results showed that significant differences were detected in the genotype distribution of C/A-18 and intron 4 polymorphisms of SP-B gene between cases and controls. No significant differences were detected in the genotype distribution of C/T1580 or A/G9306 between the two groups. Haplotype analysis revealed that the frequency of A-del-C-A haplotype was higher in case group (0.12 to 0.05, P=0.003), whereas the frequency of C-inv-C-A haplotype was higher in control group (0.19 to 0.05, P=0.000). In addition, a significant difference was observed in the frequency of C-inv-T-A haplotype between the two groups. It was concluded that the polymorphisms of SP-B intron 4 and C/A-18 could be associated with BPD in Chinese Han infants, and the del allele of intron 4 and A allele of C/A-18 might be used as markers of susceptibility in the disease. Haplotype analysis indicated that the gene-gene interactions would play an important part in determining susceptibility to BPD. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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18. New Generation Synthetic Surfactants.
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Curstedt, Tore, Calkovska, andrea, and Johansson, Jan
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NEONATAL diseases ,SURFACE active agents ,PREMATURE infants ,LABORATORY rabbits ,PROTEIN analysis ,PHOSPHOLIPIDS ,THERAPEUTICS - Abstract
The treatment of preterm newborn rabbits with synthetic surfactants containing simple phospholipid mixtures and peptides gives similar tidal volumes to treatment with poractant alfa (Curosurf®). The addition of both surfactant protein B and C analogs to the phospholipid mixture will stabilize the alveoli, measured as lung gas volumes at end expiration, even if no positive end-expiratory pressure is applied. The effect on lung gas volumes seems to depend on the structure of the peptides as well as the phospholipid composition. It seems that synthetic surfactants containing two peptides and a more complex phospholipid composition will be able to replace natural surfactants within the near future, but more experiments need to be performed before any conclusion can be drawn about the ideal composition of this new generation of synthetic surfactants. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
- Published
- 2013
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19. Surfactant protein B amount and kinetics in newborn infants: an optimized procedure.
- Author
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Simonato, Manuela, Baritussio, Aldo, Vedovelli, Luca, Lamonica, Giulia, Carnielli, Virgilio Paolo, and Cogo, Paola Elisa
- Abstract
Surfactant protein B (SP-B) plays a key role in surfactant homeostasis affecting its biophysical properties and physiological function. Recently, a method to measure SP-B amount and kinetics from tracheal aspirates (TAs) became available. The main objective of this study was to improve the critical steps of the procedure to obtain a better SP-B sensitivity. We administered a 24 h continuous infusion of 1 mg/kg/h of 1
13 C-leucine to ten newborn infants. SP-B was isolated from serial TAs and its fractional synthesis rate, secretion time, peak time and half life were derived from13 C enrichment curves obtained by gas chromatography mass spectrometry. SP-B amount in TAs was also assessed. During the extraction step, acidification and organic solvent ratio optimization doubled the recovery of SP-B from TAs, so did the elongation of the propylation time (from 20 min to 1 h) with enhanced leucine derivatization yield. Measurement of13 C leucine enrichments, and therefore all SP-B kinetics parameters, were successfully calculated in all TAs samples due to the increase of SP-B yield. SP-B amount was 0.29 (0.16-0.41) % of total phospholipids with a minimum value of 0.08% belonging to one of the respiratory distress syndrome (RDS) patients. In conclusion, this new procedure enables accurate determination of SP-B kinetics even in the presence of low protein amount like in preterm RDS patients. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]- Published
- 2012
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20. Pilot trial of late booster doses of surfactant for ventilated premature infants.
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Merrill, J. D., Ballard, P. L., Courtney, S. E., Durand, D. J., Hamvas, A., Hibbs, A. M., Lu, K. W., Ryan, R. M., Reynolds, A. M., Spence, K., Steinhorn, R. H., Truog, W. E., Eichenwald, E. C., and Ballard, R. A.
- Subjects
ARTIFICIAL respiration ,BRONCHOPULMONARY dysplasia ,CYTOKINES ,FISHER exact test ,PREMATURE infants ,RESEARCH funding ,SURFACE active agents ,T-test (Statistics) ,PILOT projects ,DATA analysis software ,DISEASE risk factors - Abstract
Objective:Many premature infants at risk for bronchopulmonary dysplasia experience episodes of surfactant dysfunction with reduced surfactant protein B (SP-B). In this study, we investigated the safety and responses to booster doses of surfactant.Study Design:A total of 87 infants, 500 to 1250 g birth weight, who were ventilated at 7 to 10 days received 2 or 3 doses of Infasurf (Calfactant, Forest Pharmaceuticals, St Louis, MO, USA) within a 1-week period.Result:For 184 doses, occurrence rates of transient bradycardia (13) and plugged endotracheal tube (5) were low, and no other adverse effects were noted. Treatment transiently improved the respiratory severity score (FiO
2 × mean airway pressure), SP-B content (+75%) and surface properties of isolated surfactant. Levels of eight proinflammatory cytokines in tracheal aspirate were interrelated and unchanged from baseline after surfactant treatment.Conclusion:Booster doses of surfactant for premature infants with lung disease are safe and transiently improve respiratory status as well as composition and function of endogenous surfactant. [ABSTRACT FROM AUTHOR]- Published
- 2011
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21. JUN-CCAAT/Enhancer-Binding Protein Complexes Inhibit Surfactant-Associated Protein B Promoter Activity.
- Author
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Bein, Kiflai, Leight, Hayley, and Leikauf, George D.
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- 2011
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22. Leptin does not influence surfactant synthesis in fetal sheep and mice lungs.
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Sato, Atsuyasu, Schehr, Angelica, and Ikegami, Machiko
- Subjects
LEPTIN ,PULMONARY surfactant ,LABORATORY mice ,SHEEP as laboratory animals ,LUNG diseases ,GENE expression - Abstract
In the fetus, leptin in the circulation increases at late gestation and likely influences fetal organ development. Increased surfactant by leptin was previously demonstrated in vitro using fetal lung explant. We hypothesized that leptin treatment given to fetal sheep and pregnant mice might increase surfactant synthesis in the fetal lung in vivo. At 122-124 days gestational age (term: 150 days), fetal sheep were injected with 5 mg of leptin or vehicle using ultrasound guidance. Three and a half days after injection, preterm lambs were delivered, and lung function was studied during 30-min ventilation, followed by pulmonary surfactant components analyses. Pregnant A/J mice were given 30 or 300 mg of leptin or vehicle by intraperitoneal injection according to five study protocols with different doses, number of treatments, and gestational ages to treat. Surfactant components were analyzed in fetal lung 24 h after the last maternal treatment. Leptin injection given to fetal sheep increased fetal body weight. Control and leptin-treated groups were similar in lung function (preterm newborn lamb), surfactant components pool sizes (lamb and fetal mice), and expression of genes related to surfactant synthesis in the lung (fetal mice). Likewise, saturated phosphatidylcholine and phospholipid were normal in mice lungs with absence of circulating leptin (ob/ob mice) at all ages. These studies coincided in findings that neither exogenously given leptin nor deficiency of leptin influenced fetal lung maturation or surfactant pool sizes in vivo. Furthermore, the key genes critically required for surfactant synthesis were not affected by leptin treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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23. Glucocorticoids potentiate IL-6-induced SP-B expression in H441 cells by enhancing the JAK-STAT signaling pathway.
- Author
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Ladenburger, Andreas, Seehase, Matthias, Kramer, Boris W., Thomas, Wolfgang, Wirbelauer, Johannes, Speer, Christian P., and Kunzmann, Steffen
- Subjects
RESPIRATORY distress syndrome ,PREMATURE labor ,PROTEIN analysis ,STEROIDS ,DEXAMETHASONE - Abstract
The respiratory distress syndrome (RDS) contributes to perinatal morbidity and mortality associated with preterm birth. Surfactant protein B (SP-B) is decreased in RDS. Both maternal antenatal steroid administration and chorioamnionitis reduce the incidence and severity of RDS. An important mediator in chorioamnionitis is IL-6 using the JAK-STAT signaling pathway for signal transduction. We hypothesized that the steroids, betamethasone (BTM) and dexamethasone (DXM), and IL-6 had synergistic effects on SP-B gene expression and STAT3 phosphorylation in H441 cells. DXM and BTM increased SP-B mRNA levels by 16.5 (13.3)-fold and IL-6 alone by 2.3-fold. After 48-h exposure of cells to DXM or BTM, IL-6 caused a significantly greater increase in SP-B mRNA levels (28.1-fold) than IL-6 or glucocorticoids alone. Whereas IL-6 stimulated tyrosine phosphorylation of STAT3 in a time- and dose-dependent way, DXM and BTM had no effect on STAT3 phosphorylation. Both DXM and BTM could potentiate IL-6-induced phosphorylation of STAT3. The synergism of glucocorticoids and IL-6 on SP-B gene expression and the effect of glucocorticoids on IL-6-induced STAT3 phosphorylation could be blocked by a JAK inhibitor. Expression level analysis showed that glucocorticoids increased the expression of the IL-6-binding α-subunit receptor (IL-6R) on mRNA and protein level. Our findings could represent an example of a pulmonary regulation system in which one role of glucocorticoids is to increase the effect of a cytokine by upregulation of its receptor. The described in vitro interaction of IL-6 and glucocorticoids could help explain the clinical observation that prenatal inflammation in preterm babies with antenatal steroid administration can attenuate severity of RDS. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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24. Bedeutung der Surfactant-Proteine B und D in der Differentialdiagnostik der akuten Dyspnoe.
- Author
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Lüers, Claus, Hagenah, Gerrit, Wachter, Rolf, Kleta, Sibylle, Schaumberg, Jens, Riedel, Sebastian, Binder, Lutz, Jung, Klaus, Schmidt, Albrecht, and Pieske, Burkert
- Abstract
Copyright of Medizinische Klinik (Urban & Vogel) is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2010
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25. Synthetic Surfactant Based on Analogues of SP-B and SP-C Is Superior to Single-Peptide Surfactants in Ventilated Premature Rabbits.
- Author
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Almlén, Andreas, Walther, Frans J., Waring, Alan J., Robertson, Bengt, Johansson, Jan, and Curstedt, Tore
- Subjects
SURFACE active agents ,LABORATORY rabbits ,RABBITS ,RESPIRATORY distress syndrome ,GLYCERIN - Abstract
Background: Respiratory distress syndrome (RDS) is currently treated with surfactant preparations obtained from natural sources and attempts to develop equally active synthetic surfactants have been unsuccessful. One difference in composition is that naturally derived surfactants contain the two hydrophobic proteins SP-B and SP-C while synthetic preparations contain analogues of either SP-B or SP-C. It was recently shown that both SP-B and SP-C (or SP-C33, an SP-C analogue) are necessary to establish alveolar stability at end-expiration in a rabbit RDS model, as reflected by high lung gas volumes without application of positive end-expiratory pressure. Objectives: To study the efficacy of fully synthetic surfactants containing analogues of both SP-B and SP-C compared to surfactants with only one protein analogue. Methods: Premature newborn rabbits, treated with synthetic surfactants, were ventilated for 30 min without positive end-expiratory pressure. Tidal volumes as well as lung gas volumes at end-expiration were determined. Results: Treatment with 2% Mini-B (a short-cut version of SP-B) and 2% SP-C33, or its C-terminally truncated form SP-C30, in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol, 68:31 (w/w) resulted in median lung gas volumes of 8-9 ml/kg body weight, while animals treated with 2% Mini-B surfactant or 2% SP-C33/SP-C30 surfactant had lung gas volumes of 3-4 ml/kg, and those treated with Curosurf, a porcine surfactant, 15-17 ml/kg. In contrast, mixing SP-C33 with peptides with different distributions of positively charged and hydrophobic residues did not improve lung gas volumes. Conclusions: The data indicate that synthetic surfactants containing analogues of both SP-B and SP-C might be superior to single-peptide surfactants in the treatment of RDS. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
- Published
- 2010
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26. Thyroid Transcription Factor in Differentiating Type II Cells.
- Author
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Kolla, Venkatadri, Gonzales, Linda W., Gonzales, John, Ping Wang, Angampalli, Sreedevi, Feinstein, Sheldon I., and Ballard, Philip L.
- Published
- 2007
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27. VDUP1: a potential mediator of expansion-induced lung growth and epithelial cell differentiation in the ovine fetus.
- Author
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Filby, C. E., Hooper, S. B., Sozo, F., Zahra, V. A., Flecknoe, S. J., and Wallace, M. J.
- Subjects
MOLECULAR cell differentiation ,LUNGS ,EPITHELIAL cells ,INFLAMMATORY mediators ,CELL proliferation ,MESSENGER RNA ,PNEUMONIA - Abstract
The degree of fetal lung expansion is a critical determinant of fetal lung growth and alveolar epithelial cell (AEC) differentiation, although the mechanisms involved are unknown. As VDUP1 (vitamin D3-upregulated protein 1) can modulate cell proliferation, can induce cell differentiation, and is highly expressed in the lung, we have investigated the effects of fetal lung expansion on VDUP1 expression and its relationship to expansion-induced fetal lung growth and AEC differentiation in fetal sheep. Alterations in fetal lung expansion caused profound changes in VDUP1 mRNA levels in lung tissue. Increased fetal lung expansion significantly reduced VDUP1 mRNA levels from 100 ± 8% in control fetuses to 37 ± 4,46 ± 4, and 45 ± 9% of control values at 2,4, and 10 days of increased fetal lung expansion, respectively. Reduced fetal lung expansion increased VDUP1 mRNA levels from 100 ± 16% in control fetuses to 162 ± 16% of control values after 7 days. VDUP1 was localized to airway epithelium in small bronchioles, AECs, and some mesenchymal cells. Its expression was inversely correlated with cell proliferation during normal lung development (R< = 0.972, P < 0.002) as well as in response to alterations in fetal lung expansion (R< 0.956, P < 0.001) and was positively correlated with SP-B expression during normal lung development (R< = 0.803, P < 0.0001) and following altered lung expansion (R² = 0.817, P < 0.001). We suggest that VDUP1 may be an important mediator of expansion-induced lung cell proliferation and AEC differentiation in the developing lung. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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28. Partial SP-B deficiency perturbs lung function and causes air space abnormalities.
- Author
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Nesslein, Lori L., Melton, Kristin R., Ikegami, Machiko, Cheng-Lun Na, Wert, Susan E., Rice, Ward R., Whitsett, Jeffrey A., and Weaver, Timothy E.
- Subjects
PROTEINS ,SURFACE active agents ,LUNG injuries ,LUNGS ,CARDIOPULMONARY system ,RESPIRATORY organs - Abstract
Surfactant protein B (SP-B) is required for function of newborn and adult lung, and partial deficiency has been associated with susceptibility to lung injury. In the present study, transgenic mice were produced in which expression of SP-B in type II epithelial cells was conditionally regulated. Concentrations of SP-B were maintained at 60-70% of that normally present in control. Immunostaining for SP-B demonstrated cellular heterogeneity in expression of the protein. In subsets of type II cells in which SP-B staining was decreased, immunostaining for pro-SP-C was increased and lamellar body ultrastructure was disrupted, consistent with focal SP-B deficiency. Fluorescence-activated cell sorting analyses of freshly isolated type II cells identified a population of cells with low SP-B content and a smaller population with increased SP-B content, confirming nonuniform expression of the SP-B transgene. Focal air space enlargement, without cellular infiltration or inflammation, was observed. Pressure-volume curves indicated that maximal tidal volume was unchanged; however, hysteresis was modestly altered and residual volumes were significantly decreased in the SP-B-deficient mice. Chronic, nonuniform SP-B deficiency perturbed pulmonary function and caused air space enlargement. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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29. Distinct effects of SP-B and SP-C on the uptake of surfactant-like liposomes by alveolar cells in vivo and in vitro.
- Author
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Poelma, D. L. H., Zimmermann, L. J., van Cappellen, W. A., Haitsma, J. J., Lachmann, B., and van Iwaarden, J. F.
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SURFACE active agents ,SURFACE tension ,LUNGS ,CARDIOPULMONARY system ,LIPOSOMES ,PHOSPHOLIPIDS - Abstract
The effects of surfactant protein B (SP-B) and SP-C on the uptake of surfactant-like liposomes by alveolar type II cells and alveolar macrophages were studied both in vivo and in vitro. In vivo, mechanically ventilated rats were intratracheally instilled with fluorescently labeled liposomes that had SP-B and/or SP-C incorporated in different concentrations. Consequently, the alveolar cells were isolated, and cell-associated fluorescence was determined using flow cytometry. The results show that the incorporation of SP-B does not influence the uptake, and it also does not in the presence of essential cofactors. The inclusion of SP-C in the liposomes enhanced the alveolar type II cells at a SP-C to lipid ratio of 2:100. If divalent cations (calcium and magnesium) were present at physiological concentrations in the liposome suspension, uptake of liposomes by alveolar macrophages was also enhanced. In vitro, the incorporation of SP-B affected uptake only at a protein-to-lipid ratio of 8:100, whereas the inclusion of SP-C in the liposomes leads to an increased uptake at a protein-to-lipid ratio of 1:100. From these results, it can be concluded that SP-B is unlikely to affect uptake of surfactant, whereas SP-C in combination with divalent cations and other solutes are capable of increasing the uptake. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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- View/download PDF
30. In vitro quantification of dexamethasone-induced surfactant protein B expression in human lung cells.
- Author
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Vidaeff, A. C., Ramin, S. M., Gilstrap III, L. C., and Alcorn, J. L.
- Subjects
SURFACE active agents ,CELL lines ,GENETIC transcription ,EPITHELIAL cells ,TISSUE culture ,HYDROCORTISONE ,ADENOCARCINOMA - Abstract
To determine whether the effect of a single 48-h exposure to dexamethasone in human lung cells is limited to 7–8 days. We used the NCI-H441 cell line, in which stability can be maintained beyond 7 days. The outcome was the stimulatory effect of dexamethasone on surfactant protein B (SP-B) gene transcription as expressed by SP-B mRNA accumulation. The experiment was conducted five times, in parallel with control. SP-B mRNA was determined at baseline, 48 h after dexamethasone exposure, and at 48-h intervals thereafter, up to 14 days, by quantitative reverse transcription polymerase chain reaction. Comparisons were made by the Mann—Whitney test. In conditions of our experiment, the inductive profile of SP-B mRNA after exposure to dexamethasone demonstrated maximal stimulation at 48 h (13-fold over control). Subsequently, there was a decline in mRNA, with return to near control levels by day 8, suggesting reversibility of dexamethasone action. Our data support the view that the surfactant-inducing properties of corticosteroids are limited to 7–8 days. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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- View/download PDF
31. Surfactant protein (SP) B associations and interactions with SP-A in white and black subjects with respiratory distress syndrome.
- Author
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Floros, Joanna, Fan, Ruzong, Diangelo, Susan, Guo, Xiaoxuan, Wert, John, and Luo, Junming
- Subjects
RESPIRATORY distress syndrome ,PROTEINS ,SURFACE active agents ,ETIOLOGY of diseases - Abstract
Abstract Background: The etiology of respiratory distress syndrome (RDS) is multifactorial and/or multigenic. Surfactant protein A (SP-A) and/or SP-B genetic variants have been identified as risk or protection factors for RDS. Methods: We genotyped subjects with and without RDS for the SP-B intron 4 size variants (invariant (inv), deletion (del), insertion (ins) and for four (–18 (A/C), 1013 (A/C), 1580 (C/T), 9306 (A/G)) SP-B single nucleotide polymorphisms (SNP), to study case–control associations in black and white subjects. We also determined whether specific SP-B variants interact with RDS susceptibility or protective SP-A variants to enhance or reduce risk for RDS. Results: Based on odds ratio: (1) the SP-B intron 4 del variant in white subjects is more of an RDS risk factor for males and for subjects of 28 weeks
2/6A 2 ) or SP-A2 (1A0 /1A0 or 1A0 /*) genotypes in subjects of certain GA and with a specific SP-B genotype (9306 (A/G) or del/*) are associated with an enhanced risk for RDS; (4) in black subjects, SP-A1 (6A3 /6A3 or 6A3 /*) genotypes in subjects of 31 weeks ≤ GA ≤ 35 weeks and with the SP-B (1580 (T/T)) genotype are associated with a reduced risk for RDS. Conclusions: The SP-B polymorphisms are important determinants for RDS. These may identify differences between black and white subjects, as well as, between males and females regarding the risk for RDS. Furthermore, SP-A susceptibility or protective alleles, in specific SP-B background, are associated, based on OR, with an increased or reduced risk for RDS. [ABSTRACT FROM AUTHOR]- Published
- 2001
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- View/download PDF
32. Function and inhibition sensitivity of the N-terminal segment of surfactant protein B (SP-B1-25) in preterm rabbits.
- Author
-
Gupta, M., Hernandez-Juviel, J. M., Waring, A. J., Waither, F. J., and Walther, F J
- Subjects
PROTEIN-based surfactants ,PULMONARY surfactant ,LABORATORY rabbits ,PREGNANCY in animals ,PULMONARY function tests ,BLOOD plasma - Abstract
Background: Surfactant protein B (SP-B) is an essential component of pulmonary surfactant, but shorter SP-B sequences may exert equivalent surface activity.Methods: We synthesised a peptide based on the amino-terminal domain of SP-B (SP-B1-25), a full length SP-B1-78, and a full length palmitoylated SP-C peptide (SP-C1-35) and compared the in vivo function and sensitivity to plasma inhibition of preparations consisting of mixtures of phospholipids with SP-B1-25 or SP-B1-78 and/or SP-C1-35 to Survanta. Preterm rabbits born at 27 days of gestation were treated at birth with surfactant and ventilated for 60 minutes. At 15 minutes half of them received plasma intratracheally. Dynamic compliance was monitored every 15 minutes and postmortem pressure-volume curves were measured to define lung mechanics.Results: Dynamic compliance and postmortem lung volumes were highest after treatment with a surfactant consisting of an SP-B peptide and SP-C1-35 or Survanta. Plasma instillation decreased dynamic compliance and lung volumes sharply, but the most effective activity was by prior instillation of surfactants containing SP-B1-25.Conclusion: These experiments suggest that the N-terminal domain of SP-B (SP-B1-25) exhibits in vitro and in vivo surface activity and is relatively insensitive to plasma inhibition. [ABSTRACT FROM AUTHOR]- Published
- 2001
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33. ARTIFICIAL SURFACTANTS BASED ON ANALOGUES OF SP-B AND SP-C.
- Author
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Johansson, Jan, Curstedt, Tore, and Robertson, Bengt
- Subjects
PEPTIDE synthesis ,PROTEIN-based surfactants - Abstract
The hydrophobic proteins SP-B and SP-C are important components of natural surfactant preparations currently used in clinical practice, and physiologically active surfactants can be made from isolated SP-B and/or SP-C reconstituted with synthetic lipids. Efforts have been made to produce these polypeptides, or analogues with similar function, by organic synthesis or expression in heterologous systems. It is important to obtain proper folding of the synthetic peptides, as required for optimal interaction with the surfactant lipids. Another issue is to avoid loss of SP-C activity due to α -helix to β -sheet transition. This latter problem can be circumvented by replacing the polyvaline stretch of SP-C with a polyleucine stretch containing a few lysines. Palmitoylation of cysteines or serines at positions 5 and 6 also seems important for the properties of SP-C. SP-B, which is too big a molecule to be easily produced by organic synthesis, apparently can be replaced in an artificial surfactant by a peptide capable of cross-linking phospholipid bilayers. The development of synthetic analogues of the surfactant proteins might make it possible to tailor artificial surfactants for specific therapeutic missions, for instance by enhancing resistance to inactivation by meconium, plasma proteins, or oxygen radicals or maximizing bacteriostatic effects. [ABSTRACT FROM AUTHOR]
- Published
- 2001
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34. Immature Circulating SP-B, Bound to HDL, Represents an Early Sign of Smoke-Induced Pathophysiological Alterations.
- Author
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Banfi, Cristina, Brioschi, Maura, Mapelli, Massimo, Gianazza, Erica, Mallia, Alice, Zoanni, Beatrice, Salvioni, Elisabetta, Gugliandolo, Paola, Capra, Nicolò, Veglia, Fabrizio, and Agostoni, Piergiuseppe
- Subjects
DISEASE risk factors ,CARDIOVASCULAR diseases risk factors ,CIGARETTE smoke ,HIGH density lipoproteins ,PULMONARY surfactant ,SMOKING ,OXIDATIVE stress - Abstract
Cigarette smoking is a major independent risk factor for cardiovascular diseases (CVD). The underlying mechanisms, however, are not clearly understood. Lungs are the primary route of exposure to smoke, with pulmonary cells and surfactant being the first structures directly exposed, resulting in the leakage of the immature proteoform of surfactant protein B (proSP-B). Herein, we evaluated whether proSP-B joined the cargo of high-density lipoprotein (HDL) proteins in healthy young subjects (n = 106) without any CVD risk factor other than smoking, and if HDL-associated proSP-B (HDL-SPB) correlated with pulmonary function parameters, systemic inflammation, and oxidative stress. At univariable analysis, HDL-SPB resulted significantly higher in smokers (2.2-fold, p < 0.001) than in non-smokers. No significant differences have been detected between smokers and non-smokers for inflammation, oxidation variables, and alveolar-capillary diffusion markers. In a multivariable model, HDL-SPB was independently associated with smoking. In conclusion, HDL-SPB is not only a precocious and sensitive index of the acute effects of smoke, but it might be also a potential causal factor in the onset of the vascular damage induced by modified HDL. These findings contribute to the emerging concept that the quality of the HDL proteome, rather than the quantity of particles, plays a central role in CVD risk protection. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
35. Synthetic peptide-containing surfactants.
- Author
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Nilsson, Gunhild, Gustafsson, Magnus, Vandenbussche, Guy, Veldhuizen, Edwin, Griffiths, William J., Sjövall, Jan, Haagsman, Henk P., Ruysschaert, Jean-Marie, Robertson, Bengt, Curstedt, Tore, and Johansson, Jan
- Subjects
PROTEIN C ,RESPIRATORY distress syndrome treatment - Abstract
Pulmonary surfactant contains two hydrophobic proteins, SP-B and SP-C. With the aim of identifying synthetic SP-B and SP-C substitutes for replacement therapy of respiratory distress syndromes, we have studied two transmembrane peptides and two amphipathic peptides that are located in the plane of a phospholipid bilayer. One amphipathic peptide was designed by changing the amino acid sequence, but not the composition or size, of the 21-residue peptide KL
4 . This peptide, designated KL2.3 from its spacing of nonpolar and polar residues, exhibited similar α-helical content as KL4 but was oriented along a phospholipid bilayer plane, in contrast to the transmembrane orientation of KL4 in the same environment. The second amphipathic peptide analyzed was succinyl-LLEKLLEWLK-amide (WMAP10). KL4 more efficiently accelerated the spreading of a mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (Pam2 GroPCho)/phosphatidylglycerol (PtdGro)/palmitic acid (PamOH), 68 : 22 : 9 (by mass), at an air/water interface than did any of the amphipathic peptides. Similarly, KL4 , but not KL2.3 , when present in an interfacial monolayer composed of Pam2 GroPCho/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol, 7 : 3 (by mass), increased lipid insertion from subphase vesicles. An SP-C analogue, SP-C(Leu), with all helical valyl residues in native SP-C replaced with Leu and the palmitoylcysteines at positions 5 and 6 replaced with Ser, but otherwise with essentially the same primary structure as the native peptide, was analyzed. SP-C(Leu) exhibited similar α-helical content as native SP-C and a transmembrane orientation and, in contrast to poly-valyl-containing synthetic peptides, it folds into a helical conformation after acid-induced denaturation. SP-C(Leu) accelerated the spreading of Pam2 GroPCho/PtdGro/PamOH, 68 : 22 : 9 (by mass), almost identically to native SP-C,... [ABSTRACT FROM AUTHOR]- Published
- 1998
- Full Text
- View/download PDF
36. Surfactant protein B 1580 polymorphism is associated with susceptibility to chronic obstructive pulmonary disease in chinese han population.
- Author
-
Ruicheng, Hu, Yongjian, Xu, and Zhenxiang, Zhang
- Abstract
Whether surfactant protein B (SP-B)-18A/C and 1580C/T polymorphism were associated with susceptibility to chronic obstructive pulmonary disease (COPD) in Chinese Han population was investigated. After genomic DNA was isolated from blood of COPD smokers and control smokers, the genotypes of SP-B-18A/C and SP-B1580C/T polymorphism loci were determined by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) respectively. The results showed that there was significant difference in genotypes distribution frequency of SP-B1580C/T polymorphism locus between COPD smokers and control smokers. C→T mutation rate (including TT homozygote and CT heterozygote) in COPD smokers was higher than in control smokers (57.9% vs 41.7%, x
2 , P<0.05), whereas there was no significant difference in genotypes distribution frequency of SP-B1580-18A/C locus between COPD smokers and control smokers. The allele frequency (29.1%) of SP-B1580-18A/C locus is lower than T allel (70.9%) in Chinese Han Population, and the distribution was different from that in Mexican, in which, the A and T allele frequencies were 85% and 15% respectively. It was concluded that SP-B1580 T allele was probably associated with increased susceptibility to COPD in Chinese Han population; The polymorphism of SP-B-18A/C locus maybe varied with race. [ABSTRACT FROM AUTHOR]- Published
- 2004
- Full Text
- View/download PDF
37. Surfactant Protein B Deficiency Induced High Surface Tension: Relationship between Alveolar Micromechanics, Alveolar Fluid Properties and Alveolar Epithelial Cell Injury.
- Author
-
Rühl, Nina, Lopez-Rodriguez, Elena, Albert, Karolin, Smith, Bradford J, Weaver, Timothy E, Ochs, Matthias, and Knudsen, Lars
- Abstract
High surface tension at the alveolar air-liquid interface is a typical feature of acute and chronic lung injury. However, the manner in which high surface tension contributes to lung injury is not well understood. This study investigated the relationship between abnormal alveolar micromechanics, alveolar epithelial injury, intra-alveolar fluid properties and remodeling in the conditional surfactant protein B (SP-B) knockout mouse model. Measurements of pulmonary mechanics, broncho-alveolar lavage fluid (BAL), and design-based stereology were performed as a function of time of SP-B deficiency. After one day of SP-B deficiency the volume of alveolar fluid V(alvfluid,par) as well as BAL protein and albumin levels were normal while the surface area of injured alveolar epithelium S(AEinjure,sep) was significantly increased. Alveoli and alveolar surface area could be recruited by increasing the air inflation pressure. Quasi-static pressure-volume loops were characterized by an increased hysteresis while the inspiratory capacity was reduced. After 3 days, an increase in V(alvfluid,par) as well as BAL protein and albumin levels were linked with a failure of both alveolar recruitment and airway pressure-dependent redistribution of alveolar fluid. Over time, V(alvfluid,par) increased exponentially with S(AEinjure,sep). In conclusion, high surface tension induces alveolar epithelial injury prior to edema formation. After passing a threshold, epithelial injury results in vascular leakage and exponential accumulation of alveolar fluid critically hampering alveolar recruitability. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
38. All-Atom Molecular Dynamics Simulations of Dimeric Lung Surfactant Protein B in Lipid Multilayers.
- Author
-
Robichaud, Nicholas A. S., Khatami, Mohammad Hassan, Saika-Voivod, Ivan, and Booth, Valerie
- Subjects
MOLECULAR dynamics ,PULMONARY surfactant ,MULTILAYERS ,LIPIDS ,PROTEINS - Abstract
Although lung surfactant protein B (SP-B) is an essential protein that plays a crucial role in breathing, the details of its structure and mechanism are not well understood. SP-B forms covalent homodimers, and in this work we use all-atom molecular dynamics simulations to study dimeric SP-B's structure and its behavior in promoting lipid structural transitions. Four initial system configurations were constructed based on current knowledge of SP-B's structure and mechanism, and the protein maintained a helicity consistent with experiment in all systems. Several SP-B-induced lipid reorganization behaviors were observed, and regions of the protein particularly important for these activities included SP-B's "central loop" and "hinge" regions. SP-B dimers with one subunit initially positioned in each of two adjacent bilayers appeared to promote close contact between two bilayers. When both subunits were initially positioned in the same bilayer, SP-B induced the formation of a defect in the bilayer, with water penetrating into the centre of the bilayer. Similarly, dimeric SP-B showed a propensity to interact with preformed interpores in the bilayer. SP-B dimers also promoted bilayer thinning and creasing. This work fleshes out the atomistic details of the dimeric SP-B structures and SP-B/lipid interactions that underlie SP-B's essential functions. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
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