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.[1]References
- Pivotal role of CCR1-positive leukocytes in bleomycin-induced lung fibrosis in mice. Tokuda, A., Itakura, M., Onai, N., Kimura, H., Kuriyama, T., Matsushima, K. J. Immunol. (2000) [Pubmed]
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