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

• Published in: The Journal of immunology (1950) Vol. 164; no. 5; pp. 2745 - 2751
• Main Authors: Tokuda, Atsuko, Itakura, Meiji, Onai, Nobuyuki, Kimura, Hiroshi, Kuriyama, Takayuki, Matsushima, Kouji
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.03.2000
• Subjects: Animals; bleomycin; Bleomycin - toxicity; CCR1 protein; Cell Movement - immunology; Female; Immune Sera - administration & dosage; Injections, Intravenous; Leukocytes - immunology; Leukocytes - metabolism; Leukocytes - pathology; macrophage inflammatory protein 1^a; Mice; Mice, Inbred C57BL; Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - immunology; Pulmonary Fibrosis - pathology; Pulmonary Fibrosis - prevention & control; Rabbits; RANTES; Receptors, CCR1; Receptors, Chemokine - biosynthesis; Receptors, Chemokine - blood; Receptors, Chemokine - immunology; Receptors, Chemokine - physiology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.164.5.2745

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.