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.
Research Institute for Diseases of the Chest, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan. kkuwano@kokyu.med.kyushu-u.ac.jp
K
K
Kuwano
N
N
Hagimoto
M
M
Kawasaki
T
T
Yatomi
N
N
Nakamura
S
S
Nagata
T
T
Suda
R
R
Kunitake
T
T
Maeyama
H
H
Miyazaki
N
N
Hara
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