Recombinant human Fas ligand induces alveolar epithelial cell apoptosis and lung injury in rabbits

This study investigated whether recombinant human soluble Fas ligand (rhs-F asL) induces apoptosis of primary type II pneumocytes in vitro and lung inj ury in vivo. Type II cells isolated from normal rabbit lung expressed Fas o n their surface and became apoptotic after an 18-h incubation with rh-sFasL . Fas expression in normal rabbit lungs was localized by immunohistochemist ry to alveolar and airway epithelia and alveolar macrophages. The administr ation of 10 mug of rh-sFasL into the right lungs of rabbits resulted 24 h l ater in both significantly more bronchoalveolar lavage fluid total protein and significantly more tissue changes compared with those in the left lungs , which received rh-sFasL plus Fas:Ig (a fusion protein that binds and bloc ks sFasL). Tissue changes included thickening of the alveolar walls, neutro philic infiltrates, apoptotic (terminal deoxynucleotidyltransferase-mediate d dUTP nick end labeling-positive) cells in the alveolar walls, and increas ed expression of interleukin-8 by alveolar macrophages (as determined by im munohistochemistry). We conclude that the alveolar epithelium of normal rab bits expresses Fas and that sFasL induces lung injury and inflammation in r abbits.