Fas/Fas ligand system mediates epithelial injury, but not pulmonary host defenses, in response to inhaled bacteria

The Fas/Fas ligand (FasL) system has been implicated in alveolar epithelial cell apoptosis during pulmonary fibrosis and acute respiratory distress sy ndrome. However, Fas ligation can also lead to cell activation and cytokine production. The goal of this study was to determine the role of the Fas/Fa sL system in host defenses against Escherichia coli, Staphylococcus aureus, and Streptococcus pneumoniae. We administered bacteria by aerosolization i nto the lungs of Fas-deficient (lpr) mice and wild-type (C57BL/6) mice and measured bacterial clearance at 6 and 12 h. One hour prior to euthanasia, t he mice received an intraperitoneal injection of human serum albumin (HSA) for alveolar permeability determinations. At all times after bacterial chal lenges, the lungs of the lpr mice contained similar or lower numbers of bac teria than those of the C57BL/6 mice. Alveolar permeability changes, as det ermined by bronchoalveolar lavage fluid HSA concentrations, were less sever e in the lpr mice 6 h after the challenges. In response to E. coli, the lpr mice had significantly more polymorphonuclear leukocytes (PMN) and macroph age inflammatory protein 2 in the lungs, whereas histopathologic changes we re less severe. In contrast, in response to the gram-positive cocci, the lp r animals had similar or lower numbers of PMN. We conclude that the Fas/Fas L system contributes to the development of permeability changes and tissue injury during-gram negative bacterial pneumonia. The Fas/FasL system did no t have a major role in the clearance of aerosolized bacteria from the lungs at the bacterial doses tested.