title: Intercellular adhesion molecule-1 and L-selectin regulate bleomycin-induced lung fibrosis.
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.
authors.affiliation: Department of Dermatology, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Hamaguchi
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Nishizawa
authors.forename: Masahide
authors.initials: M
authors.lastname: Yasui
authors.forename: Minoru
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kaburagi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Komura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nagaoka
authors.forename: Eriko
authors.initials: E
authors.lastname: Saito
authors.forename: Yuka
authors.initials: Y
authors.lastname: Shimada
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Takehara
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kadono
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Steeber
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Tedder
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sato
mesh_terms: D000818:Animals; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D003094:Collagen / Q000032:analysis; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D019041:L-Selectin / Q000235:genetics / Q000502:physiology*; D007958:Leukocyte Count; D008168:Lung / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D006133:Growth Substances; D012333:RNA, Messenger; D001761:Bleomycin; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; D003094:Collagen