title: CD200 maintains microglial potential to migrate in adult human retinal explant model.
abstract: OBJECTIVE
  Retinal microglia (MG) migrate in response to injury, degeneration and inflammation dependent upon both soluble and cognate signals they receive. Previously we found that lipopolysaccharide/interferon-gamma (LPS/IFNgamma) stimulation induces a paradoxical IL-10 mediated suppression of MG migration from retinal explants. Given the high expression of neuronal CD200, which can induce down regulation of CD200 receptor-positive MG activation and neuronal fractalkine expression potentially stimulating MG migration, we wished to further examine their respective roles in the maintenance of MG activation and migration.
  
  
  METHODS
  A human retinal explant model of MG migration was used. CD200 receptor and fractalkine receptor stimulation was achieved by addition to explants of CD200:Fc fusion protein and recombinant cytokine respectively, with or without LPS-IFNgamma stimulation that is known to suppress migration. Cell migration and cell activation (iNOS expression) was counted and assessed by numbers of CD45+ cells by immunofluorescence and standardised flow cytometric bead array analysis was performed for cytokine production.
  
  
  RESULTS
  Retinal explants expressed fractalkine and CX3CR1 immunohistochemically and by PCR. Addition of Fractalkine and not CD200:Fc induced MG migration from retinal explants. However LPS/IFNgamma-induced suppression of MG migration could only be restored in the presence of CD200:Fc, whilst MG remained iNOS-negative and generated IL-10.
  
  
  CONCLUSIONS
  Microglial responses are tightly governed within retina. Although MG do not classically activate following LPS/IFNgamma stimulation, their migration is sustained via CD200R stimulation maintaining their potential to migrate in response to injury.
authors.affiliation: University of Bristol, Bristol Eye Hospital, Bristol, UK.
authors.forename: Debra A
authors.initials: DA
authors.lastname: Carter
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Dick
mesh_terms: D015703:Antigens, CD; D000954:Antigens, Surface / Q000378:metabolism / Q000494:pharmacology*; D000073883:CX3C Chemokine Receptor 1; D002465:Cell Movement / Q000502:physiology*; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D017628:Microglia / Q000502:physiology*; D008954:Models, Biological; D064446:Orexin Receptors; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D012160:Retina / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; C477337:CD200R1 protein, human; D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D016207:Cytokines; D007141:Immunoglobulin Fc Fragments; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D064446:Orexin Receptors; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma; C042739:antigens, CD200