title: CCR5 blockade promotes M2 macrophage activation and improves locomotor recovery after spinal cord injury in mice.
abstract: Spinal cord injury (SCI) is considered to be primarily associated with loss of motor function and leads to activate diverse cellular mechanisms in the central nervous system to attempt to repair the damaged spinal cord tissue. Chemokine Receptor 5 (CCR5), a major co-receptor for macrophage-tropic human immunodeficiency viruses, is expressed on the surface of monocytes/macrophages, dendritic cells, activated T cells, and NK cells. Recent papers have indicated the important role of CCR5 in SCI, but the mechanism is still unknown. In our current study, CCR5 blockade displayed increased myelin sparring and enhanced SC repair process. The number of CD4(+) T cells, CD8(+) T cells, Ly6G(+) neutrophils and CD11b(+) macrophages were all significantly lower in the anti-CCR5 group than that in the control group after SCI. The IL-4 and IL-13 levels in anti-CCR5 group were markedly higher than that in control group after SCI. Correspondingly, the anti-CCR5-treated group showed increased numbers of Arg1- or CD206-expressing macrophages compared with the control IgG group. Furthermore, CCR5 blockade promoted PPARγ activation, and the increased numbers of M2 macrophages induced by CCR5 blockade were both reversed with additional PPARγ antagonist treatment. In conclusion, our present work provides evidence to support the concept that CCR5 blockade promotes M2 macrophage activation and improves locomotor recovery after SCI in mice.
authors.affiliation: Orthopedics Department Two, The Second Affiliated Hospital of Xi'an Jiaotong University, Xiwu road NO.157, 710004, Xi An, China.
authors.forename: Fengtao
authors.initials: F
authors.lastname: Li
authors.forename: Bin
authors.initials: B
authors.lastname: Cheng
authors.forename: Jian
authors.initials: J
authors.lastname: Cheng
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Haopeng
authors.initials: H
authors.lastname: Li
authors.forename: Xijing
authors.initials: X
authors.lastname: He
mesh_terms: D000813:Anilides / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D065100:CCR5 Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D008262:Macrophage Activation / Q000187:drug effects* / Q000502:physiology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D019713:Receptors, CCR5 / Q000378:metabolism*; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D065100:CCR5 Receptor Antagonists; C000592874:CCR5 protein, mouse; D019713:Receptors, CCR5