title: Crosstalk between macrophages and astrocytes affects proliferation, reactive phenotype and inflammatory response, suggesting a role during reactive gliosis following spinal cord injury.
abstract: BACKGROUND
  Large-scale macrophage infiltration and reactive astrogliosis are hallmarks of early spinal cord injury (SCI) pathology. The exact nature of the macrophage response and relationship between these phenomena have not been explored in detail. Here, we have investigated these responses using a combination of in vivo SCI models, organotypic and primary cultures.
  
  
  METHODS
  In vivo macrophage response was investigated using a contusive injury mouse model. Interactions between astrocytes and macrophages were studied in primary or organotypic cultures. Proliferation was assessed though MTT assay and nucleotide incorporation and gene expression changes through qPCR.
  
  
  RESULTS
  Seven days following contusive SCI, a mixed M1/M2 macrophage response was seen in the injury site. Conditioned medium from primary M1, but not M2, macrophages are able to induce astrocyte proliferation in both organotypic spinal cord cultures and primary astrocytes. Soluble factors from M1 macrophages induce a reactive astrocyte gene expression pattern, whereas M2 factors inhibit expression of these genes. M2-stimulated astrocytes are also able to decrease both M1 and M2 macrophage proliferation and decrease TNFα production in M1 macrophages.
  
  
  CONCLUSIONS
  These results suggest a strong role of M1 macrophages in inducing reactive astrogliosis and the existence of an astrocyte-mediated negative feedback system in order to dampen the immune response. These results, combined with the poor outcomes of the current immunosuppressive steroid treatments in SCI, indicate the need for more targeted therapies, taking into account the significantly different effects of M1 and M2 macrophages, in order to optimise outcome.
authors.affiliation: Cardiff Institute of Tissue Engineering & Repair, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Campus, Cardiff, CF14 4XY, UK. HaanN@cf.ac.uk.|Neuroscience and Mental Health Research Institute, College of Biomedical and Life Sciences, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff, CF24 4HQ, UK. HaanN@cf.ac.uk.
authors.forename: Niels
authors.initials: N
authors.lastname: Haan
authors.affiliation: Cardiff Institute of Tissue Engineering & Repair, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Campus, Cardiff, CF14 4XY, UK. ZhuB2@cardiff.ac.uk.
authors.forename: Bangfu
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Institute of Neurosciences, Fourth Military Medical University, 169 West Changle Road, Xi'an, 710032, China. jwangfm@fmmu.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Cardiff Institute of Tissue Engineering & Repair, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Campus, Cardiff, CF14 4XY, UK. WeiX1@cardiff.ac.uk.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Wei
authors.affiliation: Cardiff Institute of Tissue Engineering & Repair, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Campus, Cardiff, CF14 4XY, UK. SongB3@cardiff.ac.uk.|Department of Dermatology, No. 1 Hospital of China Medical University, Shenyang, 110001, China. SongB3@cardiff.ac.uk.
authors.forename: Bing
authors.initials: B
authors.lastname: Song
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D005911:Gliosis / Q000473:pathology / Q000503:physiopathology*; D007111:Immunity, Cellular / Q000502:physiology; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology*; D008264:Macrophages / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D014409:Tumor Necrosis Factor-alpha