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CX 3 CR1 deficiency delays acute skeletal muscle injury repair by impairing macrophage functions
Author(s) -
Zhao Wanming,
Lu Haiyan,
Wang Xingyu,
Ransohoff Richard M.,
Zhou Lan
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.14-270090
Subject(s) - cx3cr1 , macrophage , skeletal muscle , phagocytosis , inflammation , m2 macrophage , chemokine , immunology , biology , cd36 , endocrinology , medicine , chemokine receptor , receptor , biochemistry , in vitro
Adequate inflammatory response predominated by macrophage infiltration is essential to acute skeletal muscle injury repair. The majority of intramuscular macrophages express the chemokine receptor CX 3 CR1. We studied the role of CX3CR1 in regulating intramuscular macrophage number and function in acute injury repair by using a loss‐of‐function approach. Muscle injury repair was delayed in CX 3 CR1 GFP/GFP mice as compared with wild‐type (WT) controls. CX 3 CR1 was predominantly expressed by macrophages but not by myogenic cells or capillary endothelia cells in injured muscles. Intramuscular macrophage number and subset composition were not altered by CX 3 CR1 deficiency. Intramuscular macrophage phagocytosis function was impaired by CX 3 CR1 deficiency as demonstrated by increased number of necrotic fibers (+115%) and percentage of necrotic area (+204%) at 7 d, increased number of intramuscular neutrophils at 3 (+89%) but not 1 d, reduced number of phagocytosing macrophages (–12%) and phagocytosed beads within macrophages (–15%) in CX 3 CR1 GFP/GFP mice as compared with WT controls. The mRNA expression of CD36 (–50%), CD14 (–43%), IGF‐1 (–53%), and IL‐6 (–40%) was reduced in CX 3 CR1‐deficient macrophages as compared with WT controls. We conclude that CX3CR1 is important to acute skeletal muscle injury repair by regulating macrophage phagocytosis function and trophic growth factor production.—Zhao, W., Lu, H., Wang, X., Ransohoff, R. M., Zhou, L. CX 3 CR1 deficiency delays acute skeletal muscle injury repair by impairing macrophage functions. FASEB J. 30, 380‐393 (2016). www.fasebj.org