Intercellular adhesion molecule-1 and L-selectin regulate bleomycin-induced lung fibrosis.
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.
Hamaguchi
Yasuhito
Y
Department of Dermatology, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan.
Nishizawa
Yoriko
Y
Yasui
Masahide
M
Hasegawa
Minoru
M
Kaburagi
Yuko
Y
Komura
Kazuhiro
K
Nagaoka
Tetsuya
T
Saito
Eriko
E
Shimada
Yuka
Y
Takehara
Kazuhiko
K
Kadono
Takafumi
T
Steeber
Douglas A
DA
Tedder
Thomas F
TF
Sato
Shinichi
S
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
D016207:Cytokines; D006133:Growth Substances; D012333:RNA, Messenger; D001761:Bleomycin; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; D003094:Collagen