Murine macrophage chemokine receptor CCR2 plays a crucial role in macrophage recruitment and regulated inflammation in wound healing.
Murine macrophage chemokine receptor CCR2 plays a crucial role in macrophage recruitment and regulated inflammation in wound healing.
复制标题
DOI：
10.1002/eji.201747400
复制
发表时间：
2018-09
影响因子：
5.4
通讯作者：
Gallagher KA
中科院分区：
文献类型：
--
作者：
Boniakowski AE;Kimball AS;Joshi A;Schaller M;Davis FM;denDekker A;Obi AT;Moore BB;Kunkel SL;Gallagher KA
巨噬细胞在组织损伤后建立受调节的炎症反应中起关键作用。损伤后，CCR 2+单核细胞从外周血募集到伤口组织，并指导组织修复所必需的炎症的启动和消退。在慢性炎症阻止愈合的病理状态下，巨噬细胞不能转变为修复表型。使用皮肤伤口愈合的小鼠模型，我们发现CCR 2缺陷小鼠（CCR 2 −/−）在损伤后的所有时间点都表现出明显受损的伤口愈合。对CCR 2 −/−和野生型小鼠伤口的流式细胞术分析显示，CCR 2 −/−伤口中炎症Ly 6CHi招募的单核细胞/巨噬细胞显著减少。我们进一步表明，伤口巨噬细胞炎性细胞因子的产生在CCR 2 −/−伤口中减少。将mT/mG单核细胞/巨噬细胞连续转移到CCR 2 +/+和CCR 2 −/−小鼠中证明，在第2天和第4天标记的细胞在CCR 2 +/+和CCR 2 −/−小鼠中均移动到伤口。此外，来自野生型小鼠的单核细胞/巨噬细胞的过继转移恢复了正常愈合，可能是通过在CCR 2缺陷小鼠中恢复炎症反应。总之，这些数据表明，CCR 2在损伤后的募集和炎症反应中起关键作用，并且可以通过调节CCR 2来治疗性地操纵伤口修复。
Macrophages play a critical role in the establishment of a regulated inflammatory response following tissue injury. Following injury, CCR2+ monocytes are recruited from peripheral blood to wound tissue, and direct the initiation and resolution of inflammation that is essential for tissue repair. In pathologic states where chronic inflammation prevents healing, macrophages fail to transition to a reparative phenotype. Using a murine model of cutaneous wound healing, we found that CCR2-deficient mice (CCR2−/−) demonstrate significantly impaired wound healing at all time points post-injury. Flow cytometry analysis of wounds from CCR2−/− and wild type mice revealed a significant decrease in inflammatory, Ly6CHi recruited monocyte/macrophages in CCR2−/− wounds. We further show that wound macrophage inflammatory cytokine production is decreased in CCR2−/− wounds. Adoptive transfer of mT/mG monocyte/macrophages into CCR2+/+ and CCR2−/− mice demonstrated that labeled cells on days 2 and 4 traveled to wounds in both CCR2+/+ and CCR2−/− mice. Further, adoptive transfer of monocyte/macrophages from wild type mice restored normal healing, likely through a restored inflammatory response in the CCR2-deficient mice. Taken together, these data suggest that CCR2 plays a critical role in the recruitment and inflammatory response following injury, and that wound repair may be therapeutically manipulated through modulation of CCR2.
登录
查看更多内容
DOI：
10.1084/jem.20120340
发表时间：
2012-06-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hoeffel G;Wang Y;Greter M;See P;Teo P;Malleret B;Leboeuf M;Low D;Oller G;Almeida F;Choy SH;Grisotto M;Renia L;Conway SJ;Stanley ER;Chan JK;Ng LG;Samokhvalov IM;Merad M;Ginhoux F
通讯作者：
Ginhoux F
DOI：
10.1084/jem.20141539
发表时间：
2015-04-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dal-Secco D;Wang J;Zeng Z;Kolaczkowska E;Wong CH;Petri B;Ransohoff RM;Charo IF;Jenne CN;Kubes P
通讯作者：
Kubes P
影响因子：
7.7
作者：
Mirza RE;Fang MM;Ennis WJ;Koh TJ
通讯作者：
Koh TJ
影响因子：
25
作者：
Kierdorf, Katrin;Erny, Daniel;Prinz, Marco
通讯作者：
Prinz, Marco
影响因子：
4.4
作者：
Lucas, Tina;Waisman, Ari;Eming, Sabine A.
通讯作者：
Eming, Sabine A.