Department of Forensic Medicine, Wakayama Medical University, Wakayama, Japan.
Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan.
Sci Rep. 2017 Dec 4;7(1):16833. doi: 10.1038/s41598-017-17007-8.
The potential role of macrophages in pulmonary fibrosis (PF) prompted us to evaluate the roles of CX3CR1, a chemokine receptor abundantly expressed in macrophages during bleomycin (BLM)-induced PF. Intratracheal BLM injection induced infiltration of leukocytes such as macrophages into the lungs, which eventually resulted in fibrosis. CX3CR1 expression was mainly detected in the majority of macrophages and in a small portion of α-smooth muscle actin-positive cells in the lungs, while CX3CL1 was expressed in macrophages. BLM-induced fibrotic changes in the lungs were reduced without any changes in the number of leukocytes in Cx3cr1 mice, as compared with those in the wild-type (WT) mice. However, intrapulmonary CX3CR1 macrophages displayed pro-fibrotic M2 phenotypes; lack of CX3CR1 skewed their phenotypes toward M1 in BLM-challenged lungs. Moreover, fibrocytes expressed CX3CR1, and were increased in BLM-challenged WT lungs. The number of intrapulmonary fibrocytes was decreased in Cx3cr1 mice. Thus, locally-produced CX3CL1 can promote PF development primarily by attracting CX3CR1-expressing M2 macrophages and fibrocytes into the lungs.
巨噬细胞在肺纤维化（PF）中的潜在作用促使我们评估趋化因子受体 CX3CR1 的作用，该受体在博来霉素（BLM）诱导的 PF 期间在巨噬细胞中大量表达。气管内 BLM 注射诱导白细胞（如巨噬细胞）浸润到肺部，最终导致纤维化。CX3CR1 表达主要在肺中的大多数巨噬细胞和一小部分 α-平滑肌肌动蛋白阳性细胞中检测到，而 CX3CL1 在巨噬细胞中表达。与野生型（WT）小鼠相比，Cx3cr1 小鼠的肺部 BLM 诱导的纤维化变化减少，而白细胞数量没有变化。然而，肺内的 CX3CR1 巨噬细胞表现出促纤维化的 M2 表型；在 BLM 挑战的肺部中缺乏 CX3CR1 会使它们的表型向 M1 倾斜。此外，纤维母细胞表达 CX3CR1，并且在 BLM 挑战的 WT 肺部中增加。Cx3cr1 小鼠肺部的肺内纤维母细胞数量减少。因此，局部产生的 CX3CL1 主要通过吸引表达 CX3CR1 的 M2 巨噬细胞和纤维母细胞进入肺部来促进 PF 发展。
