Essential involvement of the CX3CL1-CX3CR1 axis in bleomycin-induced pulmonary fibrosis via regulation of fibrocyte and M2 macrophage migration.
Essential involvement of the CX3CL1-CX3CR1 axis in bleomycin-induced pulmonary fibrosis via regulation of fibrocyte and M2 macrophage migration.
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DOI：
10.1038/s41598-017-17007-8
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发表时间：
2017-12-04
影响因子：
4.6
通讯作者：
Kondo T
中科院分区：
文献类型：
--
作者：
Ishida Y;Kimura A;Nosaka M;Kuninaka Y;Hemmi H;Sasaki I;Kaisho T;Mukaida N;Kondo T
巨噬细胞在肺纤维化（PF）中的潜在作用促使我们评估CX 3CR 1的作用，CX 3CR 1是博来霉素（BLM）诱导的PF期间在巨噬细胞中大量表达的趋化因子受体。CX 3CR 1主要在肺中的大多数巨噬细胞和小部分α-平滑肌肌动蛋白阳性细胞中检测到，而CX 3CL 1在巨噬细胞中表达。与野生型（WT）小鼠相比，BLM诱导的肺部纤维化变化减少，而Cx 3cr 1 −/−小鼠的白细胞数量无任何变化。然而，肺内CX 3CR 1+巨噬细胞显示促纤维化M2表型;在BLM激发的肺中，CX 3CR 1的缺乏使其表型偏向M1。此外，纤维细胞表达CX 3CR 1，并在BLM激发的WT肺中增加。Cx 3cr 1 −/−小鼠肺内纤维细胞数量减少。因此，局部产生的CX 3CL 1主要通过吸引表达CX 3CR 1的M2巨噬细胞和纤维细胞进入肺部来促进PF的发展。
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.
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影响因子：
3.6
作者：
Lopez-de la Mora DA;Sanchez-Roque C;Montoya-Buelna M;Sanchez-Enriquez S;Lucano-Landeros S;Macias-Barragan J;Armendariz-Borunda J
通讯作者：
Armendariz-Borunda J
影响因子：
4.4
作者：
Ishida, Yuko;Hayashi, Takahito;Kondo, Toshikazu
通讯作者：
Kondo, Toshikazu
影响因子：
4.4
作者：
El-Shazly, A;Berger, P;Tunon-de-Lara, JM
通讯作者：
Tunon-de-Lara, JM
影响因子：
4.4
作者：
Ishida, Yuko;Gao, Ji-Liang;Murphy, Philip M.
通讯作者：
Murphy, Philip M.
影响因子：
4.3
作者：
Kropski JA;Lawson WE;Young LR;Blackwell TS
通讯作者：
Blackwell TS