title: CD8+ phagocytes in focal ischemia of the rat brain: predominant origin from hematogenous macrophages and targeting to areas of pannecrosis.
abstract: We have recently described a novel population of CD8+ phagocytes that are strongly recruited to focal ischemic lesions of the rat brain but absent from axotomized central fiber tracts. To assess the relative contribution of infiltrating macrophages and resident microglia to the CD8+ phagocyte response, we selectively depleted peripheral macrophages by systemic administration of dichloromethylene diphosphonate-filled liposomes prior to the induction of permanent ischemia by photothrombosis of cortical microvessels. Macrophage depletion led to a dramatic reduction but not complete abolishment of CD8+ cells in the ensuing infarcts. Systemic administration of monoclonal antibody Ox-8 eliminated CD8+ cells from peripheral lymphoid organs but had no effect on CD8+ phagocytes in the ischemic brain lesions. To further characterize the lesion conditions inducing the recruitment of CD8+ phagocytes, we induced mild focal ischemia by transient occlusion of the middle cerebral artery that leads to a core infarction with ischemic pannecrosis surrounded by areas with selective neuronal cell death. Recruitment of CD8+ phagocytes was restricted to areas of ischemic pannecrosis. In areas undergoing selective neuronal loss microglia up-regulated complement receptor-3, exhibited ED1 immunoreactivity (indicating phagocytic activity), and to some extent expressed CD4, but not CD8 antigens. In conclusion our present study shows that CD8+ phagocytes in focal brain ischemia are predominantly derived from hematogenous macrophages and selectively target to areas of ischemic pannecrosis.
authors.affiliation: Department of Neurology and Center for Biological and Medical Research, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schroeter
authors.forename: S
authors.initials: S
authors.lastname: Jander
authors.forename: I
authors.initials: I
authors.lastname: Huitinga
authors.forename: G
authors.initials: G
authors.lastname: Stoll
mesh_terms: D000818:Animals; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D051926:Basigin; D001798:Blood Proteins; D002545:Brain Ischemia / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000276:immunology* / Q000378:metabolism; D004002:Clodronic Acid / Q000494:pharmacology; D053331:Ectodysplasins; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D017628:Microglia / Q000276:immunology* / Q000378:metabolism; D009336:Necrosis; D010586:Phagocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D001798:Blood Proteins; C102624:Bsg protein, Gallus gallus; C079432:Bsg protein, rat; D015704:CD4 Antigens; D016827:CD8 Antigens; D053331:Ectodysplasins; D005904:Glial Fibrillary Acidic Protein; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D004002:Clodronic Acid; D051926:Basigin