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Intercellular Adhesion Molecule-1 and L-Selectin Regulate Bleomycin-Induced Lung Fibrosis

Authors
Journal
American Journal Of Pathology
0002-9440
Publisher
Elsevier
Publication Date
Volume
161
Issue
5
Identifiers
DOI: 10.1016/s0002-9440(10)64439-2
Keywords
  • Icam-1 And L-Selectin In Pulmonary Fibrosis
Disciplines
  • Medicine

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)-β1 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-β1. This suggests that these adhesion molecules are potential therapeutic targets for inhibiting human pulmonary fibrosis.

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