  STUDY OF THE INTERACTION BETWEEN FLUORESCENT PDMAEMA AND BLOOD CELLSLombart, François  ; Flebus, Luca ; Vervecken, Jennifer et alPoster (2012, November 22) Detailed reference viewed: 4 (3 ULg) Overexpression of CD39 in mouse airways promotes bacteria induced inflammationTheatre, Emilie ; ; et alin Journal of Immunology (2012), 189(4), 1966-1974 In airways, the ecto-nucleoside triphosphate diphosphohydrolase CD39 plays a central role in the regulation of physiological mucosal nucleotide concentrations and likely contributes to the control of ... [more ▼] In airways, the ecto-nucleoside triphosphate diphosphohydrolase CD39 plays a central role in the regulation of physiological mucosal nucleotide concentrations and likely contributes to the control of inflammation because accelerated ATP metabolism occurs in chronic inflammatory lung diseases.We sought to determine whether constant elevated CD39 activity in lung epithelia is sufficient to cause inflammation and whether this affects the response to acute LPS or Pseudomonas aeruginosa exposure. We generated transgenic mice overexpressing human CD39 under the control of the airway-specific Clara cell 10-kDa protein gene promoter. Transgenic mice did not develop any spontaneous lung inflammation. However, intratracheal instillation of LPS resulted in accelerated recruitment of neutrophils to the airways of transgenic mice. Macrophage clearance was delayed, and the amounts of CD8+ T and B cells were augmented. Increased levels of keratinocyte chemoattractant, IL-6, and RANTES were produced in transgenic lungs. Similarly, higher numbers of neutrophils and macrophages were found in the lungs of transgenic mice infected with P. aeruginosa, which correlated with improved bacteria clearance. The transgenic phenotype was partially and differentially restored by coinstillation of P2X1 or P2X7 receptor antagonists or of caffeine with LPS. Thus, a chronic increase of epithelial CD39 expression and activity promotes airway inflammation in response to bacterial challenge by enhancing P1 and P2 receptor activation. [less ▲] Detailed reference viewed: 14 (7 ULg)ATP-gated P2X1 ion channels protect from endotoxemia by dampening neutrophil activationLecut, Christelle ; Faccinetto, Céline ; Delierneux, Céline et alin Journal of Thrombosis and Haemostasis [=JTH] (2012), 10(3), 453-65 Background: In sepsis, extracellular ATP, secreted by activated platelets and leukocytes, may contribute to the crosstalk between hemostasis and inflammation. Previously, we showed that, in addition to ... [more ▼] Background: In sepsis, extracellular ATP, secreted by activated platelets and leukocytes, may contribute to the crosstalk between hemostasis and inflammation. Previously, we showed that, in addition to their role in platelet activation, ATP-gated P2X1 ion channels are involved in promoting neutrophil chemotaxis. <br />Objectives: To elucidate the contribution of P2X1 ion channels to sepsis and associated disturbance of hemostasis. <br />Methods: We used P2X1-/- mice in a model of lipopolysaccharide (LPS)-induced sepsis. Hemostasis and inflammation parameters were analysed together with outcome. Mechanisms were further studied ex vivo using mouse and human blood or isolated neutrophils and monocytes. <br />Results: P2X1-/- mice were more susceptible to LPS-induced shock than wild-type mice despite normal cytokine production. Plasma levels of thrombin-antithrombin complexes were higher, thrombocytopenia was worsened and whole blood coagulation time was markedly reduced, pointing to aggravated hemostasis disturbance in the absence of P2X1. However, whole blood platelet aggregation occurred normally and P2X1-/- macrophages displayed normal levels of total tissue factor activity. We found that P2X1-/- neutrophils produced higher amounts of reactive oxygen species. Increased amounts of myeloperoxidase were released in the blood of LPS-treated P2X1-/- mice, and circulating neutrophils and monocytes expressed higher levels of CD11b. Neutrophil accumulation into the lungs was also significantly augmented, as was lipid peroxidation in the liver. Desensitization of P2X1 ion channels led to increased activation of human neutrophils and enhanced formation of platelet-leukocyte aggregates. [less ▲] Detailed reference viewed: 27 (19 ULg) |
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