Fas (CD95) Induces Alveolar Epithelial Cell Apoptosis in Vivo

摘要: Activation of the Fas/FasL system induces apoptosis susceptible cells, but may also lead to nuclear factor kappaB activation. Our goal was determine whether local Fas activation produces acute lung injury by inducing alveolar epithelial cell and generating inflammatory responses. Normal mice (C57BL/6) deficient in (lpr) were treated intranasal instillation Fas-activating monoclonal antibody (mAb) Jo2 or an irrelevant control mAb, studied 6 24 hours later using bronchoalveolar lavage (BAL), histopathology, DNA nick-end-labeling assays, electron microscopy. with mAb had significant increases BAL protein at hours, neutrophils as compared lpr mAb. Neutrophil recruitment preceded increased mRNA expression for tumor necrosis factor-alpha, macrophage protein-1alpha, protein-2, chemotactic protein-1, interleukin-6, not interferon-gamma, transforming growth factor-ss, RANTES, eotaxin, IP-10. Lung sections from Jo2-treated normal showed neutrophilic infiltrates, septal thickening, hemorrhage, terminal dUTP nick-end-labeling-positive cells septae airspaces. Type II pneumocyte confirmed vivo results inflammation, be important pathogenesis injury.