Intercellular adhesion molecule-1 and L-selectin regulate bleomycin-induced lung fibrosis.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Hamaguchi, Y; Nishizawa, Y; Yasui, M; Hasegawa, M; Kaburagi, Y; Komura, K; Nagaoka, T; Saito, E; Shimada, Y; Takehara, K; Kadono, T; Steeber, DA; Tedder, TF; Sato, S

Published Date

  • November 2002

Published In

Volume / Issue

  • 161 / 5

Start / End Page

  • 1607 - 1618

PubMed ID

  • 12414509

Pubmed Central ID

  • PMC1850777

International Standard Serial Number (ISSN)

  • 0002-9440

Digital Object Identifier (DOI)

  • 10.1016/S0002-9440(10)64439-2


  • eng

Conference Location

  • United States