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Contribution of activated platelets to plasma IL-27 levels
Hind Hamzeh-Cognasse, Pauline Damien, Kim Nguyen, Fabrice Zeni, Bruno Pozzetto, Fabrice Cognasse, Olivier Garraud
Critical Care , 2013, DOI: 10.1186/cc11925
Abstract: IL: interleukin; TRAP: thrombin receptor activating peptide.The authors declare that they have no competing interests.The authors thank MA Eyraud and CA Arthaud for technical assistance. This work was supported by the EFS (grant APR2010-No10) the ANR (grant ANR-12- JSV1), the ART, and the 'Les Amis de Rémi' Association; France. In accordance with French regulations, platelets were obtained from regular blood donors who signed a form indicating that they do not preclude the use of their sample for medical research.
A flow cytometry technique to study intracellular signals NF-κB and STAT3 in peripheral blood mononuclear cells
Sandrine Lafarge, Hind Hamzeh-Cognasse, Patricia Chavarin, Christian Genin, Olivier Garraud, Fabrice Cognasse
BMC Molecular Biology , 2007, DOI: 10.1186/1471-2199-8-64
Abstract: The present investigation aimed at developing a flow cytometry technique to study transcription factors in various cellular types such as mixtures of B-cells, T-lymphocytes and monocytes/macrophages stimulated in steady state conditions (in other words, as peripheral blood mononuclear cells). To achieve this goal, a two step procedure was carried out; the first one consisted of stimulating PBMCs with IL1β, sCD40L and/or IL10 in such a manner that optimal stimulus was found for each cell subset (and subsequent signal transduction, therefore screened by specific ELISA); the second step consisted of assessing confirmation and fine delineation of technical conditions by specific Western-Blotting for either NF-κB or STAT products. We then went on to sensitize the detection technique for mixed cells using 4 color flow cytometry.In response to IL1β, or IL10, the levels of phosphorylated NF-κB and STAT3 – respectively – increased significantly for all the studied cell types. In contrast, B-cells and monocytes/macrophages – but, interestingly, not T-lymphocytes (in the context of PBMCs) – responded significantly to sCD40L by increasing phosphorylated NF-κB.Cytokines have essential roles in positive, negative and regulatory control of immune responses in every compartment. The biological functions of cytokines mainly depend on cytokine-mediated gene activation or repression. Studies on gene induction by different cytokines led to the discovery of several signalling pathways including NF-κB, STAT and others [1,2].Various types of specific or innate stimuli activate and phosphorylate the latent cytoplasmic NF-κB/IκB complex, which is ensued by the proteolysis of IκB. The NF-κB p65 sub-unit is then released; it is translocated to the nucleus and binds the genes containing κB sites which in turn, upregulates the expression of these gene products [2-6]. A large variety of molecules are able to activate NF-κB such as PAMPs, IL1, TNF, CD40L, BAFF [2,5]. Among activated transcription
Direct contact of platelets and their released products exert different effects on human dendritic cell maturation
Hind Hamzeh-Cognasse, Fabrice Cognasse, Sabine Palle, Patricia Chavarin, Thomas Olivier, Olivier Delézay, Bruno Pozzetto, Olivier Garraud
BMC Immunology , 2008, DOI: 10.1186/1471-2172-9-54
Abstract: Confocal microscopy showed the attachment of PLTs to DC membranes. The DC receptor involved in this interactions was found to be CD162. In addition, we observed that DCs co-cultured with PLTs in filter-separated compartments acquired a mature phenotype (high CD80, CD86, and intermediate CD83 expression; IL-12(p70) production; efficient stimulation of autologous CD4+ T cell proliferation), while DCs co-cultured with PLTs in the same compartment did not undergo phenotypic maturation, did not secrete IL-12(p70) or IL-1β, but instead induced moderate Th2-polarized T cell proliferation.These data indicate that (i) PLTs secrete a soluble DC-activating factor that was demonstrated not to be soluble CD40-Ligand (CD154; as could have been expected from in vivo and previous in vitro work) but to be nucleotide, and (ii) that cell-to-cell contact did not induce DC maturation, possibly because nucleotide release by PLTs was prevented by direct contact with DCs. This work demonstrates that PLTs are active elements of the immune system that might play a role in balancing the ability of DCs to polarize T cell responses, therefore making them critical factors in transfusion processes.Dendritic cells (DCs) are sentinels of the immune system, involved in innate and adaptive immunity, the role of which is to guard the periphery for signs of foreign invasion. Recognition of pathogens by immature DCs is mediated by a set of receptors that includes Toll-like receptors (TLRs) [1], Fc-receptors [2], and C-type lectins [3]. Upon a "danger signal", immature DCs develop into mature immunostimulatory DCs. The DC maturation program includes a change in the expression profile of chemokine receptors, enabling the maturing DCs to migrate toward draining lymph nodes [4].Maturing DCs overexpress costimulatory molecules (CD80, CD83, and CD86) and molecules involved in antigen presentation (Major Histocompatibility Complex class I and II) on their membranes. Matured DCs promote CD4+ or CD8+ T cell and
A Computerized Prediction Model of Hazardous Inflammatory Platelet Transfusion Outcomes
Kim Anh Nguyen, Hind Hamzeh-Cognasse, Marc Sebban, Elisa Fromont, Patricia Chavarin, Lena Absi, Bruno Pozzetto, Fabrice Cognasse, Olivier Garraud
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0097082
Abstract: Background Platelet component (PC) transfusion leads occasionally to inflammatory hazards. Certain BRMs that are secreted by the platelets themselves during storage may have some responsibility. Methodology/Principal Findings First, we identified non-stochastic arrangements of platelet-secreted BRMs in platelet components that led to acute transfusion reactions (ATRs). These data provide formal clinical evidence that platelets generate secretion profiles under both sterile activation and pathological conditions. We next aimed to predict the risk of hazardous outcomes by establishing statistical models based on the associations of BRMs within the incriminated platelet components and using decision trees. We investigated a large (n = 65) series of ATRs after platelet component transfusions reported through a very homogenous system at one university hospital. Herein, we used a combination of clinical observations, ex vivo and in vitro investigations, and mathematical modeling systems. We calculated the statistical association of a large variety (n = 17) of cytokines, chemokines, and physiologically likely factors with acute inflammatory potential in patients presenting with severe hazards. We then generated an accident prediction model that proved to be dependent on the level (amount) of a given cytokine-like platelet product within the indicated component, e.g., soluble CD40-ligand (>289.5 pg/109 platelets), or the presence of another secreted factor (IL-13, >0). We further modeled the risk of the patient presenting either a febrile non-hemolytic transfusion reaction or an atypical allergic transfusion reaction, depending on the amount of the chemokine MIP-1α (<20.4 or >20.4 pg/109 platelets, respectively). Conclusions/Significance This allows the modeling of a policy of risk prevention for severe inflammatory outcomes in PC transfusion.
Specific Antibody Production by Blood B Cells is Retained in Late Stage Drug-na?ve HIV-infected Africans
Lydie Béniguel,Evelyne Bégaud,Fabrice Cognasse,Philippe Gabrié,Christophe D. Mbolidi,Mary A. Marovich,Céline Cazorla,Frédéric Lucht,Christian Genin,Olivier Garraud
Clinical and Developmental Immunology , 2004, DOI: 10.1080/10446670410001722104
Abstract: Unseparated peripheral blood mononuclear cells (PBMCs) obtained from drug-na?ve African individuals living in a context of multi-infections and presenting with high viral load (VL), were cultured in vitro and tested for their ability to produce antibodies (Abs) reacting with HIV-1 antigens. Within these PBMCs, circulating B cells were differentiated in vitro and produced IgG Abs against not only ENV, but also GAG and POL proteins. Under similar experimental conditions, HAART treated patients produced Abs to ENV proteins only. The in vitro antibody production by drug-na?ve individuals' PBMCs depended on exogenous cytokines (IL-2 and IL-10) but neither on the re-stimulation of reactive cells in cultures by purified HIV-1-gp 160 antigen nor on the re-engagement of CD40 surface molecules. Further, it was not abrogated by the addition of various monoclonal Abs (mAbs) to co-stimulatory molecules. This suggests that the in vitro antibody production by drug-na?ve individuals' PBMCs resulted from the maturation of already envelope and core antigen-primed, differentiated B cells, presumably pre-plasma cells, which are not known to circulate at homeostasy. As in vitro produced Abs retained the capacity of binding antigen and forming complexes, this study provides pre-clinical support for functional humoral responses despite major HIV- and other tropical pathogen-induced B cell perturbations.
Tissue-Specific B-Cell Dysfunction and Generalized Memory B-Cell Loss during Acute SIV Infection
Sandrine Peruchon, Nada Chaoul, Chantal Burelout, Benoit Delache, Patricia Brochard, Pascale Laurent, Fabrice Cognasse, Sophie Prévot, Olivier Garraud, Roger Le Grand, Yolande Richard
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0005966
Abstract: Background Primary HIV-infected patients display severe and irreversible damage to different blood B-cell subsets which is not restored by highly efficient anti-retroviral therapy (HAART). Because longitudinal investigations of primary HIV-infection is limited by the availability of lymphoid organs, we studied the tissue-specific B-cell dysfunctions in acutely simian immunodeficiency virus (SIV) mac251-infected Cynomolgus macaques. Methods and Findings Experiments were performed on three groups of macaques infected for 14, 21 or 28 days and on three groups of animals treated with HAART for two-weeks either initiated at 4 h, 7 or 14 days post-infection (p.i.). We have simultaneously compared changes in B-cell phenotypes and functions and tissue organization of B-cell areas in various lymphoid organs. We showed that SIV induced a steady decline in SIgG-expressing memory (SIgD?CD27+) B-cells in spleen and lymph nodes during the first 4 weeks of infection, concomitant to selective homing/sequestration of B-cells to the small intestine and spleen. SIV non-specific Ig production was transiently increased before D14p.i., whereas SIV-specific Ig production was only detectable after D14p.i., coinciding with the presence of CD8+ T-cells and IgG-expressing plasma cells within germinal centres. Transient B-cell apoptosis on D14p.i. and commitment to terminal differentiation contributed to memory B-cell loss. HAART abrogated B-cell apoptosis, homing to the small intestine and SIV-specific Ig production but had minimal effect on early Ig production, increased B-cell proportions in spleen and loss of memory B-cells. Therefore, virus–B-cell interactions and SIV-induced inflammatory cytokines may differently contribute to early B-cell dysfunction and impaired SIV/HIV-specific antibody response. Conclusions These data establish tissue-specific impairments in B-cell trafficking and functions and a generalized and steady memory B-cell loss in secondary lymphoid organs. Characterization of underlying mechanisms would be helpful in designing new therapeutic strategies to dampen B-cell activation and increases HIV/SIV specific antibody response.
Identification of Germinal Center B Cells in Blood from HIV-infected Drug-naive Individuals in Central Africa
Lydie Béniguel,Evelyne Bégaud,Fabrice Cognasse,Philippe Gabrié,Christophe D. Mbolidi,Odile Sabido,Mary A. Marovich,Christiane deFontaine,Anne Frésard,Frédéric Lucht,Christian Genin,Olivier Garraud
Clinical and Developmental Immunology , 2004, DOI: 10.1080/10446670410001670454
Abstract: To better understand the pathophysiology of B cell populations—the precursors of antibody secreting cells—during chronic human immunodeficiency virus (HIV) infection, we examined the phenotype of circulating B cells in newly diagnosed Africans. We found that all African individuals displayed low levels of naive B cells and of memory-type CD27
Hammerhead Ribozymes: True Metal or Nucleobase Catalysis? Where Is the Catalytic Power from?
Fabrice Leclerc
Molecules , 2010, DOI: 10.3390/molecules15085389
Abstract: The hammerhead ribozyme was first considered as a metalloenzyme despite persistent inconsistencies between structural and functional data. In the last decade, metal ions were confirmed as catalysts in self-splicing ribozymes but displaced by nucleobases in self-cleaving ribozymes. However, a model of catalysis just relying on nucleobases as catalysts does not fully fit some recent data. Gathering and comparing data on metal ions in self-cleaving and self-splicing ribozymes, the roles of divalent metal ions and nucleobases are revisited. Hypothetical models based on cooperation between metal ions and nucleobases are proposed for the catalysis and evolution of this prototype in RNA catalysis.
Versión real y versión monetaria de una economía de mercado artesanal
Lecturas de Economía , 2008,
Abstract: the handcraft market represents the social division of work because it is referred to the exchange between separated producers; unlike pure exchange and capitalist economies, the handcraft economy integrates production but gets rid off the technical division of work. this paper displays both real and monetary models of the handcraft market where each consumer-producer generalist, maximizes his utility function. in the first model a "general market economy" arises, which is related to relative equilibrium prices, whereas in the second one, the monetary model, a "particular market economy" arises, which is linked to absolute disequilibrium prices.
Los juegos antropologicos de Saint-Louis
Delsahut, Fabrice;
Revista Brasileira de Ciências do Esporte , 2011, DOI: 10.1590/S0101-32892011000400002
Abstract: in1904, in the louisiana purchase exposition, the olympic games couldn't escape the rise in the racist ideologies of the 20th century and they contributed to the discussing of the athletic merit of the different races. their organizers set up special competitions, called for the occasion ? anthropology days ?, reserved for those who were considered as primitives by the segregationist america of that time. the impact of the race studies on the ways of thinking sport, contrary to what the different chairmen of the ioc tried hard to make believe during the new decades, was not only an unfortunate moment in the history of the olympic movement. we shall make some forecasts regarding the influence of that interracial athletic show in the united states but also in the world, in particular through the role of the press. the anthropology days surely allowed a certain perception of otherness and limited the integration of native peoples in the world sports fabric.
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