title: Adoptive transfer of M2 macrophages promotes locomotor recovery in adult rats after spinal cord injury.
abstract: Classically activated pro-inflammatory (M1) and alternatively activated anti-inflammatory (M2) macrophages populate the local microenvironment after spinal cord injury (SCI). The former type is neurotoxic while the latter has positive effects on neuroregeneration and is less toxic. In addition, while the M1 macrophage response is rapidly induced and sustained, M2 induction is transient. A promising strategy for the repair of SCI is to increase the fraction of M2 cells and prolong their residence time. This study investigated the effect of M2 macrophages induced from bone marrow-derived macrophages on the local microenvironment and their possible role in neuroprotection after SCI. M2 macrophages produced anti-inflammatory cytokines such as interleukin (IL)-10 and transforming growth factor β and infiltrated into the injured spinal cord, stimulated M2 and helper T (Th)2 cells, and produced high levels of IL-10 and -13 at the site of injury. M2 cell transfer decreased spinal cord lesion volume and resulted in increased myelination of axons and preservation of neurons. This was accompanied by significant locomotor improvement as revealed by Basso, Beattie and Bresnahan locomotor rating scale, grid walk and footprint analyses. These results indicate that M2 adoptive transfer has beneficial effects for the injured spinal cord, in which the increased number of M2 macrophages causes a shift in the immunological response from Th1- to Th2-dominated through the production of anti-inflammatory cytokines, which in turn induces the polarization of local microglia and/or macrophages to the M2 subtype, and creates a local microenvironment that is conducive to the rescue of residual myelin and neurons and preservation of neuronal function.
authors.affiliation: Central Laboratory, The First Affiliated Hospital of Bengbu Medical College, Anhui 233004, PR China; Department of Physiology, Bengbu Medical College, Anhui 233030, PR China.
authors.forename: Shan-Feng
authors.initials: SF
authors.lastname: Ma
authors.affiliation: Anhui Key Laboratory of Tissue Transplantation, The First Affiliated Hospital of Bengbu Medical College, Anhui 233004, PR China.
authors.forename: Yue-Juan
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Anhui Key Laboratory of Tissue Transplantation, The First Affiliated Hospital of Bengbu Medical College, Anhui 233004, PR China.
authors.forename: Jing-Xing
authors.initials: JX
authors.lastname: Zhang
authors.affiliation: Anhui Key Laboratory of Tissue Transplantation, The First Affiliated Hospital of Bengbu Medical College, Anhui 233004, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Shen
authors.affiliation: Anhui Key Laboratory of Tissue Transplantation, The First Affiliated Hospital of Bengbu Medical College, Anhui 233004, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Anhui Key Laboratory of Tissue Transplantation, The First Affiliated Hospital of Bengbu Medical College, Anhui 233004, PR China.
authors.forename: Jian-Sheng
authors.initials: JS
authors.lastname: Zhou
authors.affiliation: Anhui Key Laboratory of Tissue Transplantation, The First Affiliated Hospital of Bengbu Medical College, Anhui 233004, PR China.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Hu
authors.affiliation: Central Laboratory, The First Affiliated Hospital of Bengbu Medical College, Anhui 233004, PR China; Anhui Key Laboratory of Tissue Transplantation, The First Affiliated Hospital of Bengbu Medical College, Anhui 233004, PR China. Electronic address: lhz233003bmc@gmail.com.
authors.forename: He-Zuo
authors.initials: HZ
authors.lastname: Lü
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D005260:Female; D007249:Inflammation; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D008124:Locomotion; D008264:Macrophages / Q000276:immunology* / Q000637:transplantation; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology; D051381:Rats; D020127:Recovery of Function / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013119:Spinal Cord Injuries / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D018418:Th2 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha
chemical_list: C000594089:IL1B protein, rat; D018793:Interleukin-13; D053583:Interleukin-1beta; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat
keywords: Adoptive transfer; Locomotor recovery; Macrophage polarization; Microenvironment; Spinal cord injury