title: Microglia and macrophages express tumor necrosis factor receptor p75 following middle cerebral artery occlusion in mice.
abstract: The proinflammatory and potential neurotoxic cytokine tumor necrosis factor (TNF) is produced by activated CNS resident microglia and infiltrating blood-borne macrophages in infarct and peri-infarct areas following induction of focal cerebral ischemia. Here, we investigated the expression of the TNF receptors, TNF-p55R and TNF-p75R, from 1 to 10 days following permanent occlusion of the middle cerebral artery in mice. Using quantitative polymerase chain reaction (PCR), we observed that the relative level of TNF-p55R mRNA was significantly increased at 1-2 days and TNF-p75R mRNA was significantly increased at 1-10 days following arterial occlusion, reaching peak values at 5 days, when microglial-macrophage CD11b mRNA expression was also increased. In comparison, the relative level of TNF mRNA was significantly increased from 1 to 5 days, with peak levels 1 day after arterial occlusion. In situ hybridization revealed mRNA expression of both receptors in predominantly microglial- and macrophage-like cells in the peri-infarct and subsequently in the infarct, and being most marked from 1 to 5 days. Using green fluorescent protein-bone marrow chimeric mice, we confirmed that TNF-p75R was expressed in resident microglia and blood-borne macrophages located in the peri-infarct and infarct 1 and 5 days after arterial occlusion, which was supported by Western blotting. The data show that increased expression of the TNF-p75 receptor following induction of focal cerebral ischemia in mice can be attributed to expression in activated microglial cells and blood-borne macrophages.
authors.affiliation: Medical Biotechnology Center, Winsloewparken 25, University of Southern Denmark, Odense, DK-5000, Denmark. klambertsen@health.sdu.dk
authors.forename: K L
authors.initials: KL
authors.lastname: Lambertsen
authors.forename: B H
authors.initials: BH
authors.lastname: Clausen
authors.forename: C
authors.initials: C
authors.lastname: Fenger
authors.forename: H
authors.initials: H
authors.lastname: Wulf
authors.forename: T
authors.initials: T
authors.lastname: Owens
authors.forename: F
authors.initials: F
authors.lastname: Dagnaes-Hansen
authors.forename: M
authors.initials: M
authors.lastname: Meldgaard
authors.forename: B
authors.initials: B
authors.lastname: Finsen
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology; D020520:Brain Infarction / Q000378:metabolism* / Q000503:physiopathology; D018845:CD11 Antigens / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D005911:Gliosis / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D049452:Green Fluorescent Proteins; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000503:physiopathology; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism*; D020768:Middle Cerebral Artery / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000235:genetics*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D018183:Transplantation Chimera; D053319:Tumor Necrosis Factor Decoy Receptors / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D018845:CD11 Antigens; D016207:Cytokines; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; C517634:Ngfr protein, mouse; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; D049452:Green Fluorescent Proteins; C069521:recombinant human tumor necrosis factor-binding protein-1