P167 Essential role of CX3CR1 in bleomycin-induced pulmonary fibrosis through regulation of bone marrow-derived fibocyte infiltration

Abstract

Introduction Bone marrow-derived cells are known to play important roles in repair/regeneration of injured tissues, but their roles in pathological fibrosis are less clear. Here, we report a crucial role for CX3C chemokine receptor 1 (CX3CR1) in the recruitment of lung fibrocytes. Methods An intratracheal injection of bleomycin into wild-type mice caused a massive infiltration of leukocyte subsets, such as neutrophils, T lymphocytes, and macrophages, followed by the development of diffuse pulmonary fibrosis with accumulation of fibrocytes characterized by CD45+/collagen type I+ cells. Results Intrapulmonary CX3CR1 and its ligand CX3CL1 expression were enhanced significantly and remained at elevated levels until pulmonary fibrosis developed. Compared with wild-type mice, collagen deposition was attenuated in CX3CR1−/− mice with reduced number of lung fibrocytes although bleomycin increased leukocyte infiltration to a similar extent in wild-type and CX3CR1−/− mice, implying that less intrapulmonary recruitment of fibrocytes directly correlated with decreased collagen deposition in CX3CR1 deficiency. Furthermore, bone marrow transplantation from CX3CR1−/− to wild-type mice, but not that from wild-type to CX3CR1−/− mice, recapitulated the phenotypes in CX3CR1−/−- mice. Conclusion: These results demonstrated that CX3CL1-CX3CR1 interaction was involved in bleomycin-induced recruitment of bone marrow-derived fibrocytes and subsequent development of pulmonary fibrosis.