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Experimental studies have reported that aerobic exercise after asthma induction reduces lung inflammation and remodeling. Nevertheless, no experimental study has analyzed whether regular/moderate aerobic training before the induction of allergic asthma may prevent these inflammatory and remodeling processes. For this purpose, BALB/c mice ( n = 96) were assigned into non-trained and trained groups. Trained animals ran on a motorized treadmill at moderate intensity, 30 min/day, 3 times/week, for 8 weeks, and were further randomized into subgroups to undergo ovalbumin sensitization and challenge or receive saline using the same protocol. Aerobic training continued until the last challenge. Twenty-four hours after challenge, compared to non-trained animals, trained mice exhibited: (a) increased systolic output and left ventricular mass on echocardiography; (b) improved lung mechanics; (c) decreased smooth muscle actin expression and collagen fiber content in airways and lung parenchyma; (d) decreased transforming growth factor ( TGF)-β levels in bronchoalveolar lavage fluid ( BALF) and blood; (e) increased interferon ( IFN)-γ in BALF and interleukin ( IL)-10 in blood; and (f) decreased IL-4 and IL-13 in BALF. In conclusion, regular/moderate aerobic training prior to allergic asthma induction reduced inflammation and remodeling, perhaps through increased IL-10 and IFN-γ in tandem with decreased Th2 cytokines. [ABSTRACT FROM AUTHOR]

Eur J Clin Invest 2010; 40 (2): 110–120 Background Collagen V shows promise as an inducer of interstitial lung fibrosis in experimental systemic sclerosis (SSc). Materials and methods Remodelling of the pulmonary interstitium was evaluated based on the clinical data and open lung biopsies from 15 patients with SSc. Normal lung tissues obtained from eight individuals who died of traumatic injuries were used as control group. Immunofluorescence, immunohistochemistry, morphometry, tri-dimensional reconstruction and a real-time polymerase chain reaction were used to evaluate the quantity, structure and molecular chains of collagen V. The impact of these markers was tested on clinical data. Results The main difference in collagen V content between SSc patients and the control group was an increased, abnormal and distorted fibre deposition in the alveolar septa and the pre-acinar artery wall. The lungs from SSc patients presented [ α1(V)] and [ α2(V)] mRNA chain expression increased, but [ α2(V)] was proportionally increased compared with the control group. High levels of collagen V were inversely associated with vital capacity ( r = −0·72; P = 0·002), forced vital capacity ( r = −0·76; P < 0·001), forced expiratory volume in 1-s ( r = −0·89; P < 0·001) and diffusing capacity for carbon monoxide ( r = −0·62; P = 0·04). Conclusions Abnormal collagen V fibres are overproduced in lungs from SSc patients and may play an important role in the pathogenesis of the disease as this molecule regulates tissue collagen assembly. The aberrant histoarchitecture observed in SSc can be related to the overexpression of the [α2(V)] gene of unknown origin. [ABSTRACT FROM AUTHOR]

Background and Aims: To test whether different degrees of immunologic and fibrotic airway remodeling processes occur in idiopathic interstitial pneumonias (IIPs), with impact on functional tests and survival, we studied the collagen/elastic system and immune cell density in the bronchiolar interstitium of lungs with the major types of IIPs. Materials and Methods: Histochemistry, immunohistochemistry and morphometric analysis were used to evaluate collagen/elastic fibers and immune cells in the bronchiolar interstitium of open lung biopsies of patients with cryptogenic organizing pneumonia [COP/organizing pneumonia (OP) = 10], acute interstitial pneumonia [AIP/diffuse alveolar damage (DAD) = 20], nonspecific interstitial pneumonia (NSIP/NSIP = 20) and idiopathic pulmonary fibrosis/usual interstitial pneumonia (UIP) = 20. Results: OP lungs presented a significant increase in collagenous/elastic fibers and in the total density of immune cells in the bronchiolar interstitium compared to controls, DAD, NSIP and UIP. We observed a significant increase in CD4, CD8 and CD20 lymphocytes, as well as in neutrophils, macrophages and plasma cells in OP. The increased amount of elastic fibers in the bronchiolar interstitium from OP lungs has a direct association with forced vital capacity ( FVC) ( rs = 0.99, P = 0.03). The most important survival predictor was CD20+ lymphocytes in the bronchiolar interstitium. In decreasing order, patients with UIP [Odds Ratio (OR) = 35.01], high forced expiratory volume in 1 s ( FEV1)/ FVC FVC (OR = 7.01), increased CD20+ lymphocytes (OR = 4.44) and collagenous/elastic fiber densities (OR = 2.03 and OR = 1.49, respectively) in the bronchiolar interstitium were those who had the greatest risk of death, followed by those with AIP, NSIP and COP. Conclusion: Different degrees of immunologic and fibroelastotic airway remodeling processes occur in the major types of IIPs with impact on physiological tests and survival. Please cite this paper as: Parra ER, Noleto GS, Tinoco LJM, Capelozzi VL. Immunophenotyping and remodeling process in small airways of idiopathic interstitial pneumonias: functional and prognostic significance. The Clinical Respiratory Journal 2008; 2: 227–238. [ABSTRACT FROM AUTHOR]

Aims: To compare septal and vascular matrix remodelling, vascular occlusion, pulmonary function tests and survival between two groups: one with idiopathic non-specific interstitial pneumonia (NSIP) and one with NSIP associated with systemic sclerosis (SSc). Methods and results: Pulmonary biopsy specimens were examined from 40 patients, 22 with NSIP and 18 with NSIP associated with SSc. The content of septal collagen and elastic fibres, as well as the elastic fibres in the vascular interstitium, were higher in the SSc group ( P = 0.01, P = 0.001 and P < 0.0001, respectively). Among pulmonary function tests, the diffusing capacity for carbon monoxide/alveolar volume was affected to a greater extent in the SSc group (59% of the predicted value in SSc and 97% in the idiopathic group). There were no differences in collagen content of the vascular interstitium, arterial occlusion, or survival between the two groups. Conclusions: Although the fibrotic process is more intense in the SSc group, it does not affect the prognosis of these patients. Because the elastotic process is higher in the SSc group, this might suggest that autoimmune inflammatory mechanisms affecting the elastic fibre system play a greater role in the pathogenesis and pulmonary remodelling process of SSc NSIP than in idiopathic NSIP. [ABSTRACT FROM AUTHOR]

Aims: Organizing pneumonia (OP) is an inflammatory lung disease characterized histologically by intraluminal plugs involving alveolar ducts and alveoli. The aim was to examine extracellular matrix repair and remodelling in 12 cases of idiopathic OP and compare these with 11 cases of secondary OP. Methods and results: Collagen/elastic fibre density, myofibroblast proliferation, microvascular density and endothelial activity in the intraluminal plugs were evaluated by histochemistry, immunohistochemistry and morphometry. The density of the collagen system fibres was greater in plugs of idiopathic OP when compared with secondary OP ( P < 0.001). Quantification of myofibroblastic cells confirmed differences observed in patterns of immunoexpression; when compared with secondary OP, idiopathic OP contained fewer myofibroblastic cells in intraluminal plugs ( P = 0.01). Microvascular density (CD34) and endothelial activity (vascular cell adhesion molecule-1 and E-selectin) were significantly greater in secondary OP ( P < 0.05). Conclusions: Idiopathic and secondary OP show significant variation in morphological features that may represent different responses to injury. Increased collagen synthesis, low myofibroblast proliferation, poor microvascularization and minimal endothelial activity found in idiopathic OP may be more of a remodelling process than secondary OP repair. [ABSTRACT FROM AUTHOR]

Aims: Silicosis is a chronic occupational disease caused by the inhalation of free crystalline silica particles which produce inflammation and tissue destruction followed by remodelling of the extracellular matrix. Apoptosis has been implicated in the development of the initial inflammation that triggers the remodelling process. Our aim was to elucidate the importance of Fas-ligand (Fas-L) in this disorder and to study the relationship between Fas-L and several other inflammatory and fibrotic remodelling markers. Methods and results: We analysed 23 lung biopsies from silicotic patients and five controls, quantifying Fas-L and Bcl-2 expression by inflammatory cells as well as mast cells and collagen and elastic fibres. We used immunohistochemistry and morphometry to evaluate the amount of Fas-L and Bcl-2. Our analysis revealed that the silicotic lung stage was significantly related to Fas-L, mast cell and extracellular matrix remodelling. Fas-L expression was inversely associated with mast cells, collagen/elastic deposition and the silicotic lung. Conclusion: Fas-L, mast cell staining and collagen/elastic fibre quantities in silicotic lungs are strongly related to silicosis progression. [ABSTRACT FROM AUTHOR]

Rozin G F, Gomes M M, Parra E R, Kairalla R A, de Carvalho C R R&Capelozzi V L(2005)Histopathology46,413–421Collagen and elastic system in the remodelling process of major types of idiopathic interstitial pneumonias (IIP): Structural remodelling in acute and chronic idiopathic interstitial pneumonia (IIP) has been extensively investigated, but little attention has been directed to the elastic tissue in these situations. The aim of this study was to determine whether elastic deposition accompanies collagen deposition in the four major histological patterns of IIP: diffuse alveolar damage (DAD), organizing pneumonia (OP), non-specific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP).: We measured, by image analysis, the content of fibres of the collagenous and elastic systems of the alveolar septum in histological slides of open lung biopsies, using the picrosirius-polarization method and Weigert's resorcin–fuchsin stain, respectively. Five groups were studied: 10 cases of DAD; nine cases of OP; nine cases of NSIP; and 10 cases of UIP. Four normal lungs were used for comparison. The content of collagen fibres was significantly higher in UIP when compared to DAD, NSIP, OP and normal lung. The content of elastic fibres was increased in comparison with normal lungs but this was not significantly different among the histological patterns.: Acute and chronic IIP cause a similar increase in the collagen and elastic contents of the lungs, representing a process of‘fibroelastosis’ rather than an exclusive process of fibrosis. A profibrogenic mechanism is responsible for the unparallelled collagen augmentation observed in UIP subjects, the nature of which is yet to be determined. [ABSTRACT FROM AUTHOR]

Minamoto H, Antonângelo L, da Silva A G P, Gallo C P, de Andrade e Silva F B, Fenezelian S, Rodrigues O R, Jatene F, Saldiva P & Capelozzi V L (2003) Histopathology 43, 427–443 Tumour cell and stromal features in metastatic and non-metastatic non-small cell lung carcinomas Tumour cell behaviour depends on the interactions between nuclear genetic changes in the malignant cells and a stroma favourable for growth, invasion and metastasis. To evaluate such interactions, we studied the relationship between tumour cell and stromal features for proliferative factors, p53, microvessel density and metalloproteinases, controlled for the extent of the primary lesion (T1 to T4), in early (non-metastatic) and late (metastatic) non-small cell lung carcinomas (NSCLC). Variables were examined for differences and correlations in the frequency of p53, AgNOR, CD34 and MMP-9 expression in primary lesions and metastases of NSCLC using a general linear model. The patients included 58 males and 22 females (mean age 62 ± 9 years) with 19 T1 (23.8%), 40 T2 (50.0%), 14 T3 (17.5%) and seven T4 (8.8%). In late disease, AgNOR and p53 were statistically related to the extent of the primary lesion, whereas in early disease AgNOR tended to be increased in tumours without metastasis, while p53 expression tended to decrease progressively in tumours with metastasis. Microvessel density in late disease was of no statistical significance, whereas in early disease strong CD34 expression was seen in tumours with metastasis, being at its maximum in T3 primary lesions. The best marker for the extent of the lesion and its progression was MMP-9, with greater expression by tumours with metastasis than those without. Different tumour cell and stromal interactions control metastasis and therefore the biological risk of NSCLC. A panel of molecular markers, such as p53, MMP-9 and CD34 could help to identify subgroups of patients that could benefit from adjuvant therapy. [ABSTRACT FROM AUTHOR]

Aims : Pulmonary fibrosis in acute and chronic lung disease has been much investigated, but little attention has been directed at the elastic tissue in these situations. Our aim was to verify whether elastic deposition accompanies collagen deposition in the repairing process of acute and chronic lung injury. Methods and results : We measured, by image analysis, the content of fibres of the collagenous and elastic systems of the alveolar septum in histological slides sampled from autopsied lungs, using the picrosirius-polarization method and Weigert's resorcin-fuchsin stain, respectively. Five groups were studied: I, 10 normal patients; II, 10 patients with cardiogenic pulmonary oedema; III, 23 adult respiratory distress syndrome (ARDS) patients in the early phase; IV, 14 ARDS patients in the late fibroproliferative phase; and V, 10 idiopathic pulmonary fibrosis patients. The first two groups were used as controls. The content of fibres of the collagenous and elastic systems was significantly increased in groups IV and V as compared to the other groups. Conclusions : Our results indicate that deposition of elastic system fibres is present in the fibroproliferative phase of ARDS and in usual interstitial pneumonia and suggest that this event may contribute to the alveolar mechanical dysfunction and remodelling that occur in acute and chronic interstitial lung disease. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented concerning cell cycle regulator in primary lung adenocarcinoma and its hematogenous metastases.

This work demonstrates that glycerol-preserved acellular allodermis can be used as support for the proliferation of human keratinocytes and that the characteristics of this bioengineered tissue suggest its possible use as a permanent skin substitute for therapeutic challenges such as extensive burns as well as its possible use as an in vitro model for pharmacological studies. The removal of all basal membrane components during preparation of the dermal support also provides an original in vitro situation that allows observation of the reorganization of the dermal-epidermal junction. The tissue composite obtained is constituted of dermis covered by a well attached, multistratified epithelium with morphological characteristics that resemble human epidermis as evidenced by light and transmission electron microscopy, including the neoformation, albeit incomplete, of the dermal-epidermal junction. Assessment of involucrin and cytokeratin 14 expression by immunohistochemical assays established differentiation patterns. Both immerse and air-liquid interface culture systems were tested.