Essential roles of the Fas-Fas ligand pathway in the development of pulmonary fibrosis.
The Fas ligand is predominantly expressed in activated T lymphocytes and is one of the major effector molecules of cytotoxic T lymphocytes and natural killer cells. Previously, we found excessive apoptosis of epithelial cells and infiltrating lymphocytes expressing Fas ligand mRNA in the lung tissue of bleomycin-induced pulmonary fibrosis in mice. Here we demonstrated that the administration of a soluble form of Fas antigen or anti-Fas ligand antibody prevented the development of this model and that lpr and gld mice were resistant against the induction of pneumopathy. These results suggest that the Fas-Fas ligand pathway plays an essential role in the development of pulmonary fibrosis and that preventing this pathway could have therapeutic value in lung injury and fibrosis.
Kuwano
K
K
Research Institute for Diseases of the Chest, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan. kkuwano@kokyu.med.kyushu-u.ac.jp
Hagimoto
N
N
Kawasaki
M
M
Yatomi
T
T
Nakamura
N
N
Nagata
S
S
Suda
T
T
Kunitake
R
R
Maeyama
T
T
Miyazaki
H
H
Hara
N
N
D000818:Animals; D017209:Apoptosis; D001761:Bleomycin / Q000633:toxicity; D053222:Fas Ligand Protein; D006801:Humans; D006909:Hydroxyproline / Q000032:analysis; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000276:immunology; D020287:In Situ Nick-End Labeling; D007694:Killer Cells, Natural / Q000276:immunology; D008168:Lung / Q000737:chemistry / Q000473:pathology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008813:Mice, Inbred ICR; D019463:Mice, Inbred MRL lpr; D008817:Mice, Mutant Strains; D010587:Phagocytosis; D011658:Pulmonary Fibrosis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019014:fas Receptor / Q000235:genetics / Q000502:physiology*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007141:Immunoglobulin Fc Fragments; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D019014:fas Receptor; D001761:Bleomycin; D006909:Hydroxyproline