Pivotal role of CCR1-positive leukocytes in bleomycin-induced lung fibrosis in mice.
We have investigated the involvement of chemokine receptor CCR1-positive cells in bleomycin-induced lung injury, a model of pulmonary fibrosis. After bleomycin challenge in C57BL/6J mice, the expression of CCR1 mRNA increased and peaked at day 7, which paralleled to the expression of its ligands, macrophage-inflammatory protein-1 alpha and RANTES. Immunohistochemical study showed that CCR1-positive cells accumulated in the interstitial inflammatory site. Furthermore, the treatment of anti-CCR1 Ab significantly reduced the accumulation of inflammatory cells and collagen deposition, resulting in dramatic improvement of survival. These results suggest that CCR1-positive cells play significant roles in the pathogenesis of pulmonary fibrosis subsequent to bleomycin-induced lung injury, and that CCR1 could be a novel molecular target for intervention therapy against pulmonary fibrosis.
Tokuda
A
A
Department of Molecular Preventive Medicine, School of Medicine, University of Tokyo, Japan.
Itakura
M
M
Onai
N
N
Kimura
H
H
Kuriyama
T
T
Matsushima
K
K
D000818:Animals; D001761:Bleomycin / Q000633:toxicity*; D002465:Cell Movement / Q000276:immunology; D005260:Female; D007106:Immune Sera / Q000008:administration & dosage; D007275:Injections, Intravenous; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D011817:Rabbits; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000097:blood / Q000276:immunology / Q000502:physiology*
C515301:Ccr1 protein, mouse; D007106:Immune Sera; D054389:Receptors, CCR1; D019707:Receptors, Chemokine; D001761:Bleomycin