title: CX3CR1 deficiency delays acute skeletal muscle injury repair by impairing macrophage functions.
abstract: Adequate inflammatory response predominated by macrophage infiltration is essential to acute skeletal muscle injury repair. The majority of intramuscular macrophages express the chemokine receptor CX3CR1. 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 CX3CR1(GFP/GFP) mice as compared with wild-type (WT) controls. CX3CR1 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 CX3CR1 deficiency. Intramuscular macrophage phagocytosis function was impaired by CX3CR1 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 CX3CR1(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 CX3CR1-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.
authors.affiliation: *Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA; and Department of Neurosciences, Neuroinflammation Research Center, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Wanming
authors.initials: W
authors.lastname: Zhao
authors.affiliation: *Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA; and Department of Neurosciences, Neuroinflammation Research Center, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Lu
authors.affiliation: *Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA; and Department of Neurosciences, Neuroinflammation Research Center, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Xingyu
authors.initials: X
authors.lastname: Wang
authors.affiliation: *Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA; and Department of Neurosciences, Neuroinflammation Research Center, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Ransohoff
authors.affiliation: *Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA; and Department of Neurosciences, Neuroinflammation Research Center, Cleveland Clinic, Cleveland, Ohio, USA lan.zhou@mssm.edu.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D002478:Cells, Cultured; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000293:injuries / Q000378:metabolism* / Q000502:physiology; D010587:Phagocytosis; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012038:Regeneration
chemical_list: D018955:CD36 Antigens; D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D015850:Interleukin-6; D019707:Receptors, Chemokine; D007334:Insulin-Like Growth Factor I
keywords: IGF-1; chemokine; monocyte recruitment; muscle regeneration; phagocytosis