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The Journal of Immunology, 2000, 164: 2745-2751.
Copyright © 2000 by The American Association of Immunologists

Pivotal Role of CCR1-Positive Leukocytes in Bleomycin- Induced Lung Fibrosis in Mice1

Atsuko Tokuda*,{dagger}, Meiji Itakura*,{dagger}, Nobuyuki Onai*, Hiroshi Kimura{dagger}, Takayuki Kuriyama{dagger} and Kouji Matsushima2,*

* Department of Molecular Preventive Medicine, School of Medicine, University of Tokyo, Tokyo, Japan; and {dagger} Department of Chest Medicine, School of Medicine, Chiba University, Chiba, Japan

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.




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