Intercellular adhesion molecule-1 and L-selectin regulate bleomycin-induced lung fibrosis |
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Authors: | Hamaguchi Yasuhito Nishizawa Yoriko Yasui Masahide Hasegawa Minoru Kaburagi Yuko Komura Kazuhiro Nagaoka Tetsuya Saito Eriko Shimada Yuka Takehara Kazuhiko Kadono Takafumi Steeber Douglas A Tedder Thomas F Sato Shinichi |
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Institution: | Department of Dermatology, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan. |
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Abstract: | The development of bleomycin-induced lung injury, a model of pulmonary fibrosis, results from inflammatory cell infiltration, a process highly regulated by the expression of multiple adhesion molecules. At present, the identity and role of the adhesion molecules involved in the fibrotic process are unknown. Therefore, bleomycin-induced pulmonary fibrosis was examined in mice lacking L-selectin (L-selectin(-/-)) expression, intercellular adhesion molecule-1 (ICAM-1) expression, or both. After 16 days of intratracheal bleomycin challenge, collagen deposition was inhibited in both L-selectin(-/-) and ICAM-1(-/-) mice when compared with wild-type littermates. Interestingly, collagen deposition was virtually eliminated in L-selectin/ICAM-1(-/-) mice relative to either the L-selectin(-/-) or ICAM-1(-/-) mice. Decreased pulmonary fibrosis was associated with reduced accumulation of leukocytes, including neutrophils and lymphocytes. Decreased mRNA expression of proinflammatory cytokines and transforming growth factor (TGF)-beta1 paralleled the inhibition of collagen deposition. The present study indicates that L-selectin and ICAM-1 play a critical role in pulmonary fibrosis by mediating the accumulation of leukocytes, which regulate the production of proinflammatory cytokines and TGF-beta1. This suggests that these adhesion molecules are potential therapeutic targets for inhibiting human pulmonary fibrosis. |
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