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Abstract Background The interaction between the nervous system and the immune system can affect the outcome of a bacterial infection. Staphylococcus aureus skin infection is a common infectious disease, and elucidating the relationship between the nervous system and immune system may help to improve treatment strategies. Results In this study, we found that the local release of calcitonin gene-related peptide (CGRP) increased during S. aureus skin infection, and S. aureus could promote the release of CGRP from transient receptor potential cation channel subfamily V member 1 (TRPV1+) neurons in vitro. The existence of TRPV1+ neurons inhibited the recruitment of neutrophils to the infected region and regulated the polarization of macrophages toward M2 while inhibiting polarization toward M1. This reduces the level of inflammation in the infected area, which aggravates the local infection. Furthermore, this study demonstrates that TRPV1 may be a target for the treatment of S. aureus skin infections and that botulinum neurotoxin A (BoNT/A) and BIBN4096 may reverse the inhibited inflammatory effect of CGRP, making them potential therapeutics for the treatment of skin infection in S. aureus. Conclusions In S. aureus skin infection, TRPV1+ neurons inhibit neutrophil recruitment and regulate macrophage polarization by releasing CGRP. BoNT/A and BIBN4096 may be potential therapeutic agents for S. aureus skin infection.

Background: The interaction between the nervous system and the immune system can affect the outcome of a bacterial infection. Staphylococcus aureus skin infection is a common infectious disease, and elucidating the relationship between the nervous system and immune system may help to improve treatment strategies. Results: In this study, we found that the local release of calcitonin gene-related peptide (CGRP) increased during S. aureus skin infection, and S. aureus could promote the release of CGRP from transient receptor potential cation channel subfamily V member 1 (TRPV1+) neurons in vitro. The existence of TRPV1+ neurons inhibited the recruitment of neutrophils to the infected region and regulated the polarization of macrophages toward M2 while inhibiting polarization toward M1. This reduces the level of inflammation in the infected area, which aggravates the local infection. Furthermore, this study demonstrates that TRPV1 may be a target for the treatment of S. aureus skin infections and that botulinum neurotoxin A (BoNT/A) and BIBN4096 may reverse the inhibited inflammatory effect of CGRP, making them potential therapeutics for the treatment of skin infection in S. aureus. Conclusions: In S. aureus skin infection, TRPV1+ neurons inhibit neutrophil recruitment and regulate macrophage polarization by releasing CGRP. BoNT/A and BIBN4096 may be potential therapeutic agents for S. aureus skin infection. [ABSTRACT FROM AUTHOR]

Objective: This study aims to examine the relationship between the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), red blood cell distribution width (RDW), platelet distribution width (PDW) in patients diagnosed with benign, premalignant, and malignant laryngeal lesions (BLL, PLL, MLL), whether these have a predictive and prognostic value in terms of healing or progression in the follow-up of PLL. Material and Method: The files of 213 patients who were operated for laryngeal lesions between 2014 and 2020 were retrospectively analyzed and grouped as BLL, PLL, MLL according to their histopathological diagnosis. According to the lesion localization, they are also grouped as supraglottic, glottic, subglottic, and transglottic; as good and poor prognosis according to healing, recurrence, and cancer transformation status in follow-up. Age, gender, and NLR, PLR, LMR, RDW, PDW from peoperative blood samples were compared between the groups. Results: The mean age was the highest in the MLL group and the lowest in the BLL group according to the demographic characteristics of the patients (p <0.001). In gender distribution, the male gender is significantly higher in MLL and PLL groups compared to the BLL group (p <0.001). There is no significant difference between the groups in terms of NLR, PLR, LMR, RDW, and PDW values according to the diagnosis, localization, and prognostic features of the lesion. Conclusion: It was observed that NLO, PLO, LMO, RDW, and PDW values did not show a significant change according to the histopathological classification, localization, and prognosis of the disease. [ABSTRACT FROM AUTHOR]

Background: Research on the development of reliable diagnostic targets is being conducted to overcome the high prevalence and difficulty in managing periodontitis. However, despite the development of various periodontitis target markers, their practical application has been limited due to poor diagnostic accuracy. In this study, we present an improved periodontitis diagnostic target and explore its role in periodontitis. Methods: Gingival crevicular fluid (GCF) was collected from healthy individuals and periodontitis patients, and proteomic analysis was performed. The target marker levels for periodontitis were quantified in GCF samples by enzyme-linked immunosorbent assay (ELISA). Mouse bone marrow-derived macrophages (BMMs) were used for the osteoclast formation assay. Results: LC-MS/MS analysis of whole GCF showed that the level of alpha-defensin 1 (DEFA-1) was higher in periodontitis GCF than in healthy GCF. The comparison of periodontitis target proteins galactin-10, ODAM, and azurocidin proposed in other studies found that the difference in DEFA-1 levels was the largest between healthy and periodontitis GCF, and periodontitis was more effectively distinguished. The differentiation of RANKL-induced BMMs into osteoclasts was significantly reduced by recombinant DEFA-1 (rDEFA-1). Conclusions: These results suggest the regulatory role of DEFA-1 in the periodontitis process and the relevance of DEFA-1 as a diagnostic target for periodontitis. [ABSTRACT FROM AUTHOR]

Predicting stroke-associated pneumonia (SAP) is crucial for intensifying preventive measures and decreasing morbidity and mortality. This meta-analysis aims to evaluate the association between baseline neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) with SAP and to determine the strength of the association. The Web of Science, SCOPUS, and PUBMED databases were searched to find eligible studies. The standardized mean difference (SMD) and 95% confidence interval (CI) were used to evaluate the differences in NLR, MLR, and PLR levels between SAP and non-SAP patients. The meta-analysis was conducted using the software "Review Manager" (RevMan, version 5.4.1, September 2020). The random-effect model was used for the pooling analysis if there was substantial heterogeneity. Otherwise, the fixed-effect model was adopted. Twelve studies comprising 6302 stroke patients were included. The pooled analyses revealed that patients with SAP had significantly higher levels of NLR, MLR, and PLR than the non-SAP group. The SMD, 95% CI, p-value, and I2 for them were respectively reported as (0.88, 0.70–1.07,.00001, 77%); (0.94, 0.43–1.46,.0003, 93%); and (0.61, 0.47–0.75,.001, 0%). Subgroup analysis of NLR studies showed no significant differences in the effect size index between the severity of the stroke, the sample size, and the period between the stroke onset and the blood sampling. This systematic review and meta-analysis suggest that an elevated NLR, MLR, and PLR were associated with SAP, indicating that they could be promising blood-based biomarkers for predicting SAP. Large-scale prospective studies from various ethnicities are recommended to validate this association before they can be applied in clinical practice. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Rheumatologie 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.)

Background: Research on the development of reliable diagnostic targets is being conducted to overcome the high prevalence and difficulty in managing periodontitis. However, despite the development of various periodontitis target markers, their practical application has been limited due to poor diagnostic accuracy. In this study, we present an improved periodontitis diagnostic target and explore its role in periodontitis. Methods: Gingival crevicular fluid (GCF) was collected from healthy individuals and periodontitis patients, and proteomic analysis was performed. The target marker levels for periodontitis were quantified in GCF samples by enzyme-linked immunosorbent assay (ELISA). Mouse bone marrow-derived macrophages (BMMs) were used for the osteoclast formation assay. Results: LC-MS/MS analysis of whole GCF showed that the level of alpha-defensin 1 (DEFA-1) was higher in periodontitis GCF than in healthy GCF. The comparison of periodontitis target proteins galactin-10, ODAM, and azurocidin proposed in other studies found that the difference in DEFA-1 levels was the largest between healthy and periodontitis GCF, and periodontitis was more effectively distinguished. The differentiation of RANKL-induced BMMs into osteoclasts was significantly reduced by recombinant DEFA-1 (rDEFA-1). Conclusions: These results suggest the regulatory role of DEFA-1 in the periodontitis process and the relevance of DEFA-1 as a diagnostic target for periodontitis.

Scheme 1 Schematic illustration of the treatment and mechanism of Ozone@Gel for acute S. aureus OM. [Display omitted] • The Ozone@Gel is capable of continuously and steadily releasing ozone. • The Ozone@Gel can inhibit the proliferation of S. aureus and formation of biofilms. • The Ozone@Gel can enhance neutrophil antimicrobial activity to alleviate acute OM. Treatment of acute osteomyelitis (OM) poses a significant challenge because of the difficulty in removing bacteria and the aberrant innate immune responses at the infection site. Topical ozone therapy has demonstrated favorable outcomes in treating OM, but its high reactivity and short half-life severely limit its clinical application. To address this issue, a suitable ozone delivery system that can promote the therapeutic effects of topical ozone therapy in OM is needed. In this study, we developed ozone-loaded fluorinated hyaluronic acid nanoparticles embedded in a thermoresponsive hydroxypropyl chitin (HPCH) hydrogel (Ozone@Gel) for treating acute OM. The ozone-delivering nanocomposite hydrogel could release ozone continuously and stably at the injection site for over 15 days. The ozone loaded in this ozone-delivering nanocomposite hydrogel was about 100 mg/L. In vitro antibacterial experiments demonstrated that the Ozone@Gel effectively attenuated Staphylococcus aureus proliferation and reduced biofilm formation by inhibiting the expression of bacterial polysaccharide-related genes (agr, atlE, aap, icaA, and icaBC). Further, animal experiments showed that Ozone@Gel effectively reduced bacterial load at the site of infection by enhancing neutrophil antimicrobial activity, thereby alleviating the progression of acute OM. Thus, this novel therapeutic strategy based on topical ozone therapy is a promising and feasible intervention for treating acute S. aureus OM. [ABSTRACT FROM AUTHOR]

Résumé: Dans les formes sévères de la Covid-19, les réponses inflammatoires exacerbées, les dommages tissulaires subséquents, ainsi que les évènements thromboemboliques ou immunothrombotiques déclenchés par le Sars-Cov-2 sont les principales causes d'insuffisance respiratoire et de décès. Il est connu que les filets du neutrophile (NET), libérés lors d'un processus appelé NETose, peuvent se former dans les poumons suite à une infection par des virus respiratoires. Ces structures extracellulaires ont la capacité de provoquer des lésions pulmonaires et de favoriser la formation de thrombi et la fibrose, complications majeures de la Covid-19 sévère. Dans une étude récente, nous avons cherché à comprendre comment la NETose pouvait être liée aux changements immunopathologiques pulmonaires associés à des cas mortels de la maladie. Nous avons recherché ces structures NET dans les biopsies pulmonaires post-mortem de patients Covid-19. Nous avons ensuite analysé leur localisation dans les lésions et dans les différents compartiments micro-anatomiques des poumons. À cette fin, nous avons effectué une coloration par immunofluorescence de la myéloperoxydase, de l'histone citrullinée H3 et de l'acide nucléique (DAPI) sur des coupes de biopsies pulmonaires incluses dans la paraffine de quatre patients Covid-19 et de quatre patients décédés d'une cause non liée à la Covid-19. Les premiers représentaient des cas prototypiques graves et mortels de la Covid-19, caractérisés par une pneumonie et une insuffisance respiratoire fatale associées à une inflammation systémique, une neutrophilie et une coagulopathie. Nous avons détecté des NET dans les poumons de chaque patient Covid-19. Une analyse histopathologique détaillée a révélé de larges zones d'infiltration de NET dans plusieurs compartiments pulmonaires correspondant aux microthrombi artériolaires, aux zones inflammatoires riches en neutrophiles de l'interstitium pulmonaire ainsi qu'aux alvéoles ou bronchioles où elles étaient souvent colocalisées avec des dépôts occlusifs de fibrine. Une autre étude, publiée simultanément à la nôtre, a fourni les premières preuves expérimentales de l'existence d'un lien causal possible entre la NETose et les lésions pulmonaires. Même si l'implication des NET dans les évènements thrombotiques associés à la Covid-19 n'a pas encore été démontrée, ces données soutiennent l'hypothèse selon laquelle les NET représenteraient des acteurs clé des complications pulmonaires associées à la maladie. Elles suggèrent également que le ciblage des NET pourrait représenter des voies potentielles pour le traitement des réponses inflammatoires et thrombotiques à l'infection par le Sars-Cov -2. In severe Covid-19, hyperinflammatory tissue-damaging, thromboembolic or immunothrombotic responses triggered by Sars-Cov-2 are major causes of respiratory failure and death. Neutrophil extracellular traps (NETs), released by activated neutrophils during a process called NETosis, can be formed in the lungs upon infection with respiratory viruses. They have the ability to promote lung damage, thrombosis and fibrosis, three cardinal features encountered in severe Covid-19. In a recent study, we sought to understand how NETosis could relate to lung immunopathological changes associated with fatal cases of the disease. We assessed whether NET structures could be identified in post-mortem lung biopsies from Covid-19 patients, and whether they were located in particular lesions and micro-anatomical lung compartments. We performed immunofluorescence staining of myeloperoxidase, citrullinated histone H3 and nuclear acid (DAPI) on sections of paraffin-embedded lung biopsies from four Covid-19 patients who succumbed Covid-19 and from four patients who died from a Covid-19-unrelated cause. The four patients represented prototypical severe and fatal cases of Covid-19, characterized by pneumonia and fatal respiratory distress associated with signs of systemic inflammation, neutrophilia and coagulopathy. NETs were uniquely detected in the lungs of each Covid-19 patient. Detailed histopathological analysis revealed widely distributed NET-infiltrating areas encompassing several lung compartments, including arteriolar microthrombi, neutrophil-rich inflammatory areas of lung interstitium as well as alveoli or bronchioles where they often co-localized with occluding fibrin-rich deposits. Another study published simultaneously to ours provides first experimental evidence for causality between NETosis and lung injury in severe Covid-19. However, the possible involvement of NETs in thrombogenesis remains to be addressed. Notwithstanding, these data support the hypothesis that NETs may represent drivers of Covid-19-associated severe pulmonary complications, and suggest that NET-targeting approaches could represent potential avenues for the treatment of uncontrolled tissue-damaging, thrombotic or fibrotic responses to Sars-Cov-2. [ABSTRACT FROM AUTHOR]

Die transfusionsassoziierte akute Lungeninsuffizienz (TRALI) ist eine seltene, schwerwiegende Transfusionsreaktion, die durch plötzliche akute Atemnot während oder innerhalb von sechs Stunden nach einer Transfusion gekennzeichnet ist. TRALI gehörte viele Jahre zu den häufigsten Ursachen für transfusionsbedingte Todesfälle. Seit ihre Pathogenese besser erforscht ist, konnte durch spezifische Spenderselektion die Fallzahl und Todesrate deutlich gesenkt werden. Trotzdem ist Achtsamkeit geboten, denn vereinzelt gibt es immer noch tödliche Verläufe. [ABSTRACT FROM AUTHOR]

L'hétérogénéité de l'asthme dans l'enfance est caractérisée par de multiples phénotypes liés à des mécanismes physiopathologiques différents qui caractérisent les endotypes. Les sensibilisations allergéniques multiples et précoces sont associées à un risque plus élevé d'exacerbations d'asthme. Le risque de persistance de l'asthme à l'âge adulte est un phénotype d'asthme sévère notamment à début précoce avec comorbiditées allergiques multiples et/ou avec mauvaise fonction respiratoire. A l'inverse, l'inflammation des voies respiratoires à neutrophile est moins fréquente chez les enfants souffrant d'asthme et n'est pas stable au cours du temps. The heterogeneity of asthma and allergic diseases in childhood is characterized by multiple phenotypes related to different pathophysiologic mechanisms or endotypes. Early multiple carry a higher risk of severe asthma phenotype, especially in terms of asthma exacerbations. Early-onset asthma with multiple allergic comorbidities and/or poor lung function entails a risk of persistent lifelong asthma. Conversely, the neutrophilic asthma phenotype is less common in children and is not stable over time. [ABSTRACT FROM AUTHOR]

Copyright of German Journal of Sports Medicine / Deutsche Zeitschrift fur Sportmedizin is the property of Verein zur Forderung der Sportmedizin Hannover e.V. 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.)

Bien que l'évaluation de l'inflammation bronchique, par expectoration induite, permette d'identifier différents phénotypes, chez les patients asthmatiques, il n'y a que peu d'informations sur le déterminant du pattern d'inflammation bronchique chez les patients présentant un asthme professionnel par sensibilisation. Déterminer si le pattern d'inflammation bronchique, déterminé par expectoration induite, permet de définir des phénotypes cliniques distincts. Cette étude multicentrique rétrospective a été réalisée auprès de 372 patients, présentant un asthme professionnel diagnostiqué par test d'exposition spécifique, qui étaient recrutés par le biais de la cohorte du groupe European network for Phenotypique of Ocupational Asthma. Chaque patient a bénéficié d'une expectoration induite avant et après test d'exposition spécifique. L'éosinophilie bronchique était définie par un pourcentage d'éosinophiles supérieur ou égal à 3 % dans l'expectoration induite, après test d'exposition spécifique, alors que la neutrophilie bronchique était définie par un pourcentage de neutrophiles supérieur ou égal à 76 %. Au total, 268 (72 %) et 42 patients (11 %) présentaient respectivement une éosinophilie et une neutrophilie bronchique. Les analyses de régression logistique ont mis en évidence une association entre l'éosinophilie bronchique et l'exposition aux agents de haut poids moléculaire (odds ratio [OR], 1,89 ; IC 95 % 1,18–3,04), l'asthme persistant modéré (OR, 3,17 ; IC 95 %, 1,43–7,0) et l'asthme persistant sévère (OR, 2,39 ; IC 95 %, 1,06–5,43). La neutrophilie bronchique était associée à l'âge (OR pour chaque année supplémentaire, 1,04 ; IC 95 % 1,01–1,08), au genre masculin (OR, 2,83 : IC 95 %, 1,14–6,87), à l'asthme persistant léger (OR, 3,26 ; IC 95 %, 1,24–8,88), et à la dysphonie (OR, 2,83 ; IC95 %, 1,14–6,87). La majorité des patients avec un asthme professionnel par sensibilisation présentait une éosinophilie bronchique post-test d'exposition spécifique. L'éosinophilie et la neutrophilie, dans les expectorations induites, permettaient de définir des phénotypes cliniques différents, notamment en termes de sévérité et selon l'agent causal. Although the non-invasive assessment of airway inflammation through the induced sputum (IS) technique identified distinct asthma phenotypes, there is few information on the determinants of airway inflammatory pattern in sensitizer-induced occupational asthma (OA). To investigate whether the pattern of airway inflammation in IS is associated with distinct clinical phenotypes of OA. This retrospective multicentric study was conducted among 372 patients with OA confirmed by a positive specific inhalation challenge (SIC) who were recruited in the European network for the Phenotyping of OCupational Asthma cohort (2006–2018). Each patient underwent an analysis of IS before and 24 hours after the SIC. Sputum eosinophilia and neutrophilia were defined by the presence of ≥ 3% eosinophils and ≥ 76% neutrophils in sputum samples collected after the SIC. In total, 268 (72%) and 42 patients (11%) exhibited sputum eosinophilia and neutrophilia, respectively. Multivariate logistic regression analysis revealed that eosinophilia was associated with exposure to a high molecular weight agent (odds ratio [OR], 1.89; 95% CI, 1.18–3.04), moderate asthma (OR, 3.17; 95% CI, 1,43–7.0) and severe asthma (OR, 2.39; 95% CI, 1.06–5.43). Sputum neutrophilia was associated with age (OR for each additional year, 1.04; 95% CI, 1.01–1.08), male gender (OR, 2.74; 95% CI, 1,21–6.8), mild asthma (OR, 3.26; 95% CI, 1.24–8.88), and dysphonia (OR, 2.83; 95% CI, 1.14–6.87). Sputum eosinophilia post-SIC was predominant in OA patients. Sputum eosinophilia and neutrophilia were associated with distinct clinical phenotypes of OA, especially in terms of causal agents and asthma severity. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of our study was to evaluate the effect of oral taurine on the incidence of febrile episodes during chemotherapy in young adults with acute lymphoblastic leukemia. Methods: Forty young adults with acute lymphoblastic leukemia, at the beginning of maintenance course of their chemotherapy, were eligible for this study. The study population was randomized in a double blind manner to receive either taurine or placebo (2 gram per day orally). Life quality and side effects including febrile episodes were assessed using questionnaire. Data were analyzed using Pearson’s Chi square test. Results: Of total forty participants, 43.8% were female and 56.3 % were male. The mean age was 19.16±1.95 years (ranges: 16-23 years). The results indicated that the levels of white blood cells are significantly (P

Introduction: Surgical site infection (SSI) is a widely seen postoperative complication that causes a decrease in life quality and an economic burden. In this study, we aim to find the predictive values of preoperative and postoperative neutrophile lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) values for SSI., Methods: In this retrospective study, 698 patients who had total abdominal hysterectomy operations with benign indications and confirmed histopathological results were accessed. In this study, the correlation of preoperative NLR, preoperative PLR, postoperative NLR, and postoperative PLR, with the occurrence of postoperative surgical site infection complications were examined., Results: The overall SSI rate was 9.46% (n = 66) with 30 days follow-up postoperatively. Preoperative NLR and PLR values of the patients who had SSIs were significantly lower than the control group (p < 0.05). Postoperative NLR and PLR values of the patients who had SSIs were significantly higher than control group (p < 0.05). In the patients who had postoperative SSIs, the increase of the values of postoperative NLR and PLR were significantly higher than the control group (p < 0.05)., Conclusions: In our study, hematological markers of NLR and PLR were found to be independent and significant predictive markers for SSI., Competing Interests: There isn't any conflict of interest by the authors., (© 2023 Kamuzu University of Health Sciences.)

Abstract: Biodegradability of graphene is one of the fundamental parameters determining the fate of this material in vivo. Two types of aqueous dispersible graphene, corresponding to single‐layer (SLG) and few‐layer graphene (FLG), devoid of either chemical functionalization or stabilizing surfactants, were subjected to biodegradation by human myeloperoxidase (hMPO) mediated catalysis. Graphene biodegradation was also studied in the presence of activated, degranulating human neutrophils. The degradation of both FLG and SLG sheets was confirmed by Raman spectroscopy and electron microscopy analyses, leading to the conclusion that highly dispersed pristine graphene is not biopersistent. [ABSTRACT FROM AUTHOR]

Engineering self-propelled micromotors with good biocompatibility and biodegradability for actively seeking disease sites and targeted drug transport remains a huge challenge. In this study, neutrophils with intrinsic chemotaxis capability were transformed into self-guided hybrid micromotors by integrating mesoporous silica nanoparticles (MSNs) with high loading capability. To ensure the compatibility of neutrophil cells with drug-loaded MSNs, bacteria membranes derived from E. coli were coated on MSNs in advance by a camouflaging strategy. The resulting biohybrid micromotors inherited the characteristic chemotaxis capability of native neutrophils and could effectively move along the chemoattractant gradients produced by E. coli. Our studies suggest that this camouflaging approach, which favors the uptake of MSNs into neutrophils without loss of cellular activity and motility, could be used to construct synthetic nanoparticle-loaded biohybrid micromotors for advanced biomedical applications. [ABSTRACT FROM AUTHOR]

Résumé La granulomatose avec polyangéite (GPA, Wegener) est une vascularite systémique des vaisseaux de petit calibre (artères, artérioles et capillaires) qui affecte particulièrement les reins et les poumons. Dans cette pathologie auto-immune, la protéinase 3 (PR3) produite par les neutrophiles, est la cible des anti-neutrophil cytoplasmic antibodies (ANCA). Les travaux récents de notre équipe ont permis de décrypter comment la PR3 interfère avec les mécanismes de résolution de l’inflammation et dérégule le système immunitaire. En conditions normales, l’élimination des neutrophiles activés enclenche un processus anti-inflammatoire et pro-résolutif. Chez les patients GPA, la phagocytose des neutrophiles apoptotiques exprimant PR3 par les macrophages est associée à une libération massive de médiateurs pro-inflammatoires par ces derniers, en particulier l’interleukine-1, générant un microenvironnement pro-inflammatoire favorable à l’auto-immunité. Cette dérégulation immunitaire s’accompagne d’une activation des cellules dendritiques plasmacytoïdes et d’une polarisation des lymphocytes T helper (Th)2 et Th9 et Th17. Ces données récentes mettent en lumière le double rôle de la PR3, protéine auto-antigénique et auto-inflammatoire, ouvrant ainsi de potentielles pistes thérapeutiques. Granulomatosis with polyangiitis (GPA or Wegener) is a systemic vasculitis of small vessels (arteries, arterioles and capillaries) which particularly affects the kidneys and lungs. In this pathology, the proteinase 3 (PR3) produced by neutrophils is the target of anti-neutrophil cytoplasmic antibodies (ANCA). Our recent work has allowed us to decipher how PR3 interferes with the mechanisms of resolution of inflammation and deregulates the immune system. Under normal conditions, elimination of activated neutrophils triggers an anti-inflammatory and pro-resolving process. In GPA patients, phagocytosis of apoptotic neutrophils (that express PR3) by macrophages is associated with a massive release of pro-inflammatory mediators by these macrophages, particularly interleukin-1, generating a pro-inflammatory microenvironment prone to autoimmunity. This immune dysregulation is accompanied by activation of plasmacytoid dendritic cells and polarization of T helper (Th) 2, Th9 and Th17 lymphocytes. These recent data highlights the dual role of PR3, autoantigenic and auto-inflammatory protein, opening potential therapeutic pathways. [ABSTRACT FROM AUTHOR]

Ceruloplasmin, an acute-phase protein, can affect the activity of leukocytes through its various enzymatic activities and protein-protein interactions (with lactoferrin, myeloperoxidase, eosinophil peroxidase, serprocidins, and 5-lipoxygenase (5-LOX), among others). However, the molecular mechanisms of ceruloplasmin activity are not clearly understood. In this study, we tested the ability of two synthetic peptides, RPYLKVFNPR (883-892) (P1) and RRPYLKVFNPRR (882-893) (P2), corresponding to the indicated fragments of the ceruloplasmin sequence, to affect neutrophil activation. Leukotriene (LT) B4 is the primary eicosanoid product of polymorphonuclear leukocytes (PMNLs, neutrophils). We studied leukotriene synthesis in PMNLs upon interaction with Salmonella enterica serovar Typhimurium. Priming of neutrophils with phorbol 12-myristate 13-acetate (PMA) elicited the strong regulatory function of P2 peptide as a superoxide formation inducer and leukotriene synthesis inhibitor. Ceruloplasmin-derived P2 peptide appeared to be a strong inhibitor of 5-LOX product synthesis under conditions of oxidative stress. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of our study was to evaluate the effect of oral taurine on the incidence of febrile episodes during chemotherapy in young adults with acute lymphoblastic leukemia. Methods: Forty young adults with acute lymphoblastic leukemia, at the beginning of maintenance course of their chemotherapy, were eligible for this study. The study population was randomized in a double blind manner to receive either taurine or placebo (2 gram per day orally). Life quality and side effects including febrile episodes were assessed using questionnaire. Data were analyzed using Pearson's Chi square test. Results: Of total forty participants, 43.8% were female and 56.3% were male. The mean age was 19.16±1.95 years (ranges: 16-23 years). The results indicated that the levels of white blood cells are significantly (P<0.05) increased in taurine treated group. There was no elevation in blasts count. A total of 70 febrile episodes were observed during study, febrile episodes were significantly (P<0.05) lower in taurine patients in comparison to the control ones. Conclusion: The overall incidence of febrile episodes and infectious complications in acute lymphoblastic leukemia patients receiving taurine was lower than placebo group. Taurine's ability to increase leukocyte count may result in lower febrile episodes. [ABSTRACT FROM AUTHOR]

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This study aimed to determine the contrasting ecotoxicity effects of zinc on growth and photosynthesis in a neutrophilic (Chlamydomonas reinhardtii) and an extremophilic (Cyanidium caldarium) alga. Experiments were carried out to see if cells acclimated to zinc would respond differently to cells that were unexposed to zinc. The study also aimed to see if extremophiles displayed different acclimation properties to neutrophiles. Results showed that the neutrophilic alga C. reinhardtii, was more susceptible to free zinc and had a lower IC50 value than the extremophile, however its stress response protected the photosynthetic apparatus. Upon acclimation, the photosynthetic abilities of C. reinhardtii were not significantly compromised when exposed to toxic levels of free zinc. On the other hand, C. caldarium had a stress response which allowed it to tolerate significantly higher amounts of free zinc in its environment compared to C. reinhardtii , however the stress response did not protect the photosynthetic apparatus, and upon acclimation C. caldarium was no better equipped to protect its photosynthetic integrity than unexposed cells. [ABSTRACT FROM AUTHOR]

Résumé: Les vascularites à anticorps anti-cytoplasme de polynucléaire neutrophile (ANCA) regroupent trois entités distinctes : la granulomatose avec polyangéite (GPA) anciennement maladie de Wegener, la polyangéite microscopique (PAM) et la granulomatose éosinophilique avec polyangéite (GEPA) (anciennement syndrome de Churg et Strauss). Ces trois pathologies ont comme point commun d’être des vascularites impliquant des vaisseaux de petit calibre et d’être associées à une auto-immunité dirigée contre des protéines contenues dans les granules cytoplasmiques des neutrophiles. Dans cet article, nous avons résumé les éléments clés qui interviennent dans la physiopathologie de ces maladies et souligné les nouveaux concepts qui ont récemment émergé. De multiples travaux portant sur la physiopathologie de ces maladies se sont concentrés sur le rôle éventuellement pathogène des ANCA dans l’activation des neutrophiles. Cependant, la distinction entre GPA et PAM n’était pas clairement énoncée et les schémas physiopathologiques proposés insistaient principalement sur les mécanismes communs à ces pathologies. Il existe de réelles différences entre GPA et PAM, probablement liées au fait que les protéines autoantigènes cibles des ANCA, la protéinase 3 (PR3) et la myéloperoxydase (MPO), respectivement, ont des fonctions très différentes dans le neutrophile mais également dans la régulation de la réaction inflammatoire. En particulier, l’existence de granulome associée à une auto-immunité spécifique dirigée contre la protéinase 3 pourrait résulter de mécanismes propres à la GPA, comme sembleraient le montrer des travaux récents de notre équipe. [Copyright &y& Elsevier]

Résumé: Les récepteurs Fc (FcRs) sont des molécules qui reconnaissent spécifiquement les fragments Fc des différentes classes d’immunoglobulines. Quatre classes de FcRs (pour les IgG, IgA, IgE et IgM) ont été décrites à ce jour. Ils sont exprimés sur les leucocytes, essentiellement sur les phagocytes et sur les lymphocytes B. Les polynucléaires neutrophiles au repos expriment fortement deux types de FCγRS, le FCγRIIA et le FCγRIIIB, ainsi que le FcαRI (récepteur aux IgA). Par contre, ils n’expriment pas le FcεRI ou le FcμRI. Les fonctions de ces récepteurs sur le neutrophile sont multiples et essentielles dans la défense de l’hôte contre les microorganismes. Les FcRs peuvent activer ou inhiber les réponses immunitaires. Les FcRs activateurs jouent un rôle clé dans la phagocytose et la sécrétion de facteurs solubles comme des cytokines ou des substances vasoactives. L’activation des FcRs induit des voies de signalisation qui modulent la mise en route des réponses immunitaires, par exemple la production de cytokines. Certains FcRs comme le FcαRI, peuvent avoir une double fonctionnalité en utilisant leur unique motif de transduction (à ITAM) soit pour inhiber soit pour activer les réponses immunitaires, selon la structure du ligand reconnu (par exemple des IgA monomériques ou poly-mériques). Finalement, des polymorphismes dans les gènes codant pour les FcRs peuvent être impliqués dans l’initiation et/ou aggravation de certaines maladies infectieuses ou autoimmunes. Sur le polynucléaire neutrophile, ces polymorphismes peuvent générer un changement de liaison vis-à-vis de certains ligands et une réponse immunitaire altérée. [Copyright &y& Elsevier]

Diet supplementation with omega-3 fatty acids could influence the oxidative equilibrium, enhancing a pro-oxidant status. The aim was to determine the effects of diet supplementation with docosahexaenoic acid (DHA), training, and acute exercise on oxidative balance in neutrophils. Fifteen volunteer male soccer players were randomly assigned to a placebo or experimental group. The placebo group was supplemented with an almond-based beverage whereas the experimental group was supplemented with the same beverage enriched with DHA, in addition to their Mediterranean-type diet. Three blood samples were taken: in basal conditions at the beginning of the nutritional intervention and after 8 weeks of training season in basal and postexercise conditions. The training season significantly increased the antioxidant defenses of neutrophils, such as catalase, glutathione peroxidase and glutathione reductase enzyme activities; and decreased oxidative damage markers such as malondialdehyde, carbonyl and nitrotyrosine indexes. Oxidative damage markers decreased in neutrophils after acute exercise, which primed neutrophils to produce reactive oxygen and nitrogen species (RONS) after immune stimulation with zymosan or phorbol myristate acetate in trained footballers. DHA supplementation resulted in no significant effects on oxidative stress balance in neutrophils. In conclusion, DHA supplementation did not modify the adaptive response of the antioxidant system of neutrophils to training or the production of RONS induced by immune stimulation after acute exercise. [ABSTRACT FROM AUTHOR]