Soluble Fas ligand induces epithelial cell apoptosis in humans with acute lung injury (ARDS)

The goat of this study were to determine whether the Fas-dependent apoptosi s pathway is active in the lungs of patients with the acute respiratory dis tress syndrome (ARDS), and whether this pathway can contribute to lung epit helial injury. We found that soluble Fas ligand (sFasL) is present in bronc hoalveolar lavage (BAL) fluid of patients before and after the onset of ARD S, The BAL concentration of sFasL at the onset of ARDS was significantly hi gher in patients who died. BAL from patients with ARDS induced apoptosis of distal lung epithelial cells, which express Fas, and this effect was inhib ited by blocking the Fas/FasL system using three different strategies: anti -Fast mAb, anti-Fas mAb, and a Fas-Ig fusion protein. In contrast, BAL from patients at risk for ARDS had no effect on distal lung epithelial cell apo ptosis, These data indicate that sFasL is released in the airspaces of pati ents with acute lung injury and suggest that activation of the Fas/FasL sys tem contributes to the severe epithelial damage that occurs in ARDS. These data provide the first evidence that Fast can be released as a biologically active, death-inducing mediator capable of inducing apoptosis of cells of the distal pulmonary epithelium during acute lung injury.