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Am. J. Respir. Crit. Care Med., Volume 162, Number 2, August 2000, 695-700

The Fas/Fas-Ligand System Is Not Required for Bleomycin-induced Pulmonary Fibrosis in Mice

KAZUTETSU AOSHIBA, SHUJI YASUI, JUN TAMAOKI, and ATSUSHI NAGAI

First Department of Medicine, Tokyo Women's Medical University, Tokyo, Japan

Recent studies suggest that Fas-Fas-ligand (FasL) interactions play an important role in the development of lung injury and fibrosis. However, evidence to support this concept is still indirect. To determine whether Fas-FasL interaction is required for the development of bleomycin-induced pulmonary fibrosis in mice, we used Fas-deficient (lpr) and FasL-deficient (gld ) mice as animal models. After intratracheal instillation of bleomycin, we examined the lungs of mice through bronchoalveolar lavage, histologic studies, DNA nick-end labeling, and hydroxyproline assay. The development of cellular infiltrates, bronchiolar and alveolar epithelial apoptosis, and fibrosis following bleomycin instillation in the lungs in lpr mice and gld mice was similar to their development in wild-type mice. The results of this study show that bleomycin-induced pulmonary fibrosis does not require Fas-FasL interaction, and that epithelial cell apoptosis after bleomycin exposure is mediated by Fas-independent pathways.




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