Recombinant human Fas ligand induces alveolar epithelial cell apoptosis and lung injury in rabbits.
This study investigated whether recombinant human soluble Fas ligand (rh-sFasL) induces apoptosis of primary type II pneumocytes in vitro and lung injury in vivo. Type II cells isolated from normal rabbit lung expressed Fas on their surface and became apoptotic after an 18-h incubation with rh-sFasL. Fas expression in normal rabbit lungs was localized by immunohistochemistry to alveolar and airway epithelia and alveolar macrophages. The administration of 10 microg of rh-sFasL into the right lungs of rabbits resulted 24 h later 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 blocks sFasL). Tissue changes included thickening of the alveolar walls, neutrophilic infiltrates, apoptotic (terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling-positive) cells in the alveolar walls, and increased expression of interleukin-8 by alveolar macrophages (as determined by immunohistochemistry). We conclude that the alveolar epithelium of normal rabbits expresses Fas and that sFasL induces lung injury and inflammation in rabbits.
Matute-Bello
G
G
Medical Research Service, Seattle Veterans Affairs Medical Center, Seattle 98108-1597, USA.
Liles
W C
WC
Frevert
C W
CW
Nakamura
M
M
Ballman
K
K
Vathanaprida
C
C
Kiener
P A
PA
Martin
T R
TR
D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism; D008171:Lung Diseases / Q000139:chemically induced*; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D011817:Rabbits; D011994:Recombinant Proteins; D019014:fas Receptor / Q000378:metabolism
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D019014:fas Receptor