57 research outputs found

    Differential cell reaction upon Toll-like receptor 4 and 9 activation in human alveolar and lung interstitial macrophages

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    BACKGROUND: Investigations on pulmonary macrophages (MΦ) mostly focus on alveolar MΦ (AM) as a well-defined cell population. Characteristics of MΦ in the interstitium, referred to as lung interstitial MΦ (IM), are rather ill-defined. In this study we therefore aimed to elucidate differences between AM and IM obtained from human lung tissue. METHODS: Human AM and IM were isolated from human non-tumor lung tissue from patients undergoing lung resection. Cell morphology was visualized using either light, electron or confocal microscopy. Phagocytic activity was analyzed by flow cytometry as well as confocal microscopy. Surface marker expression was measured by flow cytometry. Toll-like receptor (TLR) expression patterns as well as cytokine expression upon TLR4 or TLR9 stimulation were assessed by real time RT-PCR and cytokine protein production was measured using a fluorescent bead-based immunoassay. RESULTS: IM were found to be smaller and morphologically more heterogeneous than AM, whereas phagocytic activity was similar in both cell types. HLA-DR expression was markedly higher in IM compared to AM. Although analysis of TLR expression profiles revealed no differences between the two cell populations, AM and IM clearly varied in cell reaction upon activation. Both MΦ populations were markedly activated by LPS as well as DNA isolated from attenuated mycobacterial strains (M. bovis H37Ra and BCG). Whereas AM expressed higher amounts of inflammatory cytokines upon activation, IM were more efficient in producing immunoregulatory cytokines, such as IL10, IL1ra, and IL6.CONCLUSION: AM appear to be more effective as a non-specific first line of defence against inhaled pathogens, whereas IM show a more pronounced regulatory function. These dissimilarities should be taken into consideration in future studies on the role of human lung MΦ in the inflammatory response

    Tight junctions and the modulation of barrier function in disease

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    Tight junctions create a paracellular barrier in epithelial and endothelial cells protecting them from the external environment. Two different classes of integral membrane proteins constitute the tight junction strands in epithelial cells and endothelial cells, occludin and members of the claudin protein family. In addition, cytoplasmic scaffolding molecules associated with these junctions regulate diverse physiological processes like proliferation, cell polarity and regulated diffusion. In many diseases, disruption of this regulated barrier occurs. This review will briefly describe the molecular composition of the tight junctions and then present evidence of the link between tight junction dysfunction and disease

    FaisabilitĂ© et impact du dĂ©pistage VIH chez les requĂ©rants d’asile

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    Les requĂ©rants d’asile (RA) constituent une population vulnĂ©rable, Ă  risque augmentĂ© d’infection par le VIH, de diagnostic tardif et de transmettre le virus. Cette Ă©tude vise Ă  tester la faisabilitĂ© d’un test de dĂ©pistage du VIH pour les RA arrivant dans les cantons du Valais et de Vaud afin de mieux rĂ©pondre aux recommandations suisses et internationales qui cherchent Ă  Ă©largir le dĂ©pistage afin de dĂ©tecter et traiter prĂ©cocement toute personne VIH-positive. Ceci dans son propre intĂ©rĂȘt et afin d’enrayer au mieux la transmission puisqu’une personne traitĂ©e efficacement peut ĂȘtre considĂ©rĂ©e comme non contagieuse. MĂ©thode Proposition d’un test de dĂ©pistage VIH gratuit sur une base volontaire aux RA nouvellement arrivĂ©s entre novembre 2015 et juin 2016 dans le canton du Valais et entre juin et octobre 2016 dans le canton de Vaud. Le test a Ă©tĂ© effectuĂ© lors de consultations mĂ©dicales obligatoires, aprĂšs une information Ă©crite (VS) ou orale (VD). Les RA de moins de 16 ans et les femmes enceintes ont Ă©tĂ© exclus. L’étude a Ă©tĂ© approuvĂ©e par la Commission d’éthique du canton de Vaud. Les donnĂ©es rĂ©coltĂ©es dans une base anonymisĂ©e ont Ă©tĂ© analysĂ©es et des comparaisons univariĂ©es et multivariĂ©es ont Ă©tĂ© Ă©tablies entre les donnĂ©es dĂ©mographiques et les taux d’acceptation du dĂ©pistage dans les 2 cantons. RĂ©sultats Huit-cent-sept RA se sont vus proposer un test de dĂ©pistage VIH : 451 (55.9%) en VS et 356 (44.1%) dans le canton de VD. Leur Ăąge moyen Ă©tait de 27.6 ans. Ils Ă©taient majoritairement cĂ©libataires (67.4%) et originaires d’Afrique Subsaharienne (60.8%). Le taux global d’acceptation du dĂ©pistage est de 72.2% ; 63.2% en VS, avec une diminution temporelle liĂ©e Ă  un dĂ©ficit progressif d’information, et 83.7% dans le canton de VD, avec une stabilitĂ© au cours du temps. Deux cas auparavant inconnus d’infection par le VIH ont Ă©tĂ© dĂ©couverts, 5 autres Ă©taient dĂ©jĂ  connus (prĂ©valence=0.87%). Tous ont pu rapidement ĂȘtre pris en charge par des consultations spĂ©cialisĂ©es. Le sexe masculin, l‘origine d’Afrique subsaharienne et l’inclusion dans le canton de Vaud constituaient des facteurs indĂ©pendants d’acceptation du dĂ©pistage.Conclusion Le taux d’acceptation du dĂ©pistage VIH est Ă©levĂ© chez les RA arrivant dans les cantons du VS et de VD. Les quelques cas d’infection dĂ©tectĂ©s ont pu ĂȘtre rapidement pris en charge. Les diffĂ©rences d’acceptation entre les 2 cantons apparaissent liĂ©es Ă  des diffĂ©rences dĂ©mographiques, au mode de consentement et aux moyens Ă  disposition

    Antigen presentation in the lung: dendritic cells and macrophages.

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    Antigen presentation is a required prime event before T-cell activation can occur. Cells which constitutively express major histocompatibility antigen class I or II are responsible for presenting antigens. These are essentially alveolar macrophages (AM) residing mostly in the air spaces, and dendritic cells (DC), which create a tight surveillance network just below the epithelial cells of the airways and in the loose connective tissue around the vessels or in the pleura. AM are poor antigen presenting cells compared to DC. AM when encountering foreign particles or organisms may, however, influence the degree of activity or maturation of neighbouring DC, by releasing cytokines. Thus, we will describe how the innate immune processes may influence specific immunity and perhaps Th1 and Th2 differentiation. Following the description of the differences in phenotype and functions of AM and DC, we will provide data showing that in some pathological conditions, such as sarcoidosis, AM can acquire some specificities of DC

    L'exploitation de l'eau dans le département de Gaya : des projets à contresens des besoins des populations

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    L'objectif initial du programme dans lequel ont été réalisées les études était d'analyser les conflits d'utilisation de l'eau. Il est apparu que le principal problÚme en termes d'aménagements hydrauliques pour l'approvisionnement en eau potable et l'irrigation est l'inadaptation des projets aux caractéristiques hydrologiques de la région et aux besoins des populations. La fourniture d'eau potable est un enjeu majeur, les programmes d'aménagement de puits ont privilégié un objectif d'accÚs à l'eau par la construction de puits cimentés n'offrant aucune amélioration, comparativement aux puits traditionnels, en matiÚre de qualité de l'eau. L'eau des puits modernes est en effet hautement contaminée du fait de la contamination généralisée des nappes. Les investissements en matiÚre d'approvisionnement en eau domestique ont été insuffisants par rapport aux besoins. Les investissements sont par contre hors de proportion pour ce qui concerne le développement de l'irrigation. Les agriculteurs ayant développé l'irrigation sans l'appui d'un projet ont opté pour une stratégie d'investissement à bas coût. L'investissement est de quelques centaines de millier de FCFA par hectare alors qu'il se chiffre en dizaines de million pour l'aménagement des périmÚtres hydro agricoles et à plus d'un million dans le cas du programme d'appui à la petite irrigation privée. De plus, les conditions d'attribution d'une aide financiÚre dans le cadre de ce programme excluent la grande majorité des agriculteurs

    Apoptosis and cytologic differentiation in hepatocellular carcinoma on fine needle aspiration samples.

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    OBJECTIVE: To evaluate possible alterations of the mechanisms leading to apoptosis in hepatocellular carcinoma by studying bcl-2 expression on fine needle aspiration biopsy (FNAB) samples using immunocytochemistry. STUDY DESIGN: The study was performed on a series of 84 hepatocarcinomas aspirated under ultrasound guidance. A Papanicolaou-stained smear for each case was destained and restained for bcl-2 by using the immunoperoxidase technique. bcl-2 Expression was then correlated with cytologic grading and the size of the tumor. RESULTS: In 16 cases (19%), bcl-2 immunostaining gave a specific cytoplasmic signal. Fourteen of these positive cases were well differentiated, and two were pleomorphic tumors. Six positive cases were smaller than 5 cm, 3 were larger than 5 cm, and 7 were diffuse. CONCLUSION: A significant percentage of hepatocellular carcinomas produce and accumulate bcl-2 protein in cell cytoplasm. bcl-2 Expression can be detected on destained cytologic smears. bcl-2 Expression seems to correlate with the cytologic degree of differentiation but not with the size of the tumor

    Retrospective evaluation of DNA ploidy of hepatocarcinoma on cytologic samples.

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    DNA ploidy was evaluated by image cytometry in a series of 84 hepatocellular carcinomas diagnosed by fine-needle aspiration biopsy. In the series were included eight cases originally diagnosed as suspect and reclassified as well-differentiated hepatocarcinoma. The study was retrospectively performed on Papanicolaou-destained, Feulgen-restained smears. The 5c exceeding rate and the visual interpretation of the corresponding histograms were evaluated and compared with size of the tumors, serum alpha-fetoprotein values, hepatic functional staging, and patient survival. Sixty-eight cases were aneuploid and 16 euploid (9 diploid and 7 polyploid). Four of the eight cytologically suspect cases were aneuploid. Statistical analysis showed an association between size and cytologic grading, 5c exceeding rate and cytologic grading, and between aneuploidy and multiple tumors; in a Cox multivariate DNA content analysis, aneuploidy and multiple tumors were the two prognostically significant variables. DNA ploidy evaluation by static cytometry of hepatic tumors may be useful in the diagnosis on cytologic samples and could represent an independent prognostic parameter in predicting the survival outcome of patients with hepatocellular carcinoma
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