title: CD45 isoform RB as a molecular target to oppose lipopolysaccharide-induced microglial activation in mice.
abstract: CD45 is a membrane-bound protein tyrosine phosphatase expressed on all hemopoietic cells with multiple splice variants, including RA, RB, RC and RO. Our previous studies have shown that cross-linking of CD45 with an anti-CD45 antibody markedly inhibits LPS-induced microglia activation. In order to determine which of the CD45 isoforms may be responsible for these effects, we have investigated the expression of CD45 isoforms on cultured microglial cells using flow cytometric analysis. Data reveal that CD45RB is the predominant isoform expressed in murine primary cultured microglial cells. Furthermore, incubation of these cultured cells with anti-CD45RB antibody results in a reduction of microglial activation induced by LPS as evidenced by TNF-alpha production. As a validation of these findings in vivo, brain homogenates from anti-CD45RB antibody (MG23G2)-injected animals that had been treated with LPS demonstrate a significant decrease in TNF-alpha levels compared to control mice treated with LPS plus vehicle. Taken together, these findings suggest that therapeutic agents that specifically stimulate the microglial CD45RB signaling pathway may be effective in suppressing microglial activation associated with several neurodegenerative disorders.
authors.affiliation: Neuroimmunology Laboratory, Institute for Psychiatry in Research, Department of Psychiatry and Behavioral Medicine, University of South Florida College of Medicine, 3515 East Fletcher Avenue, Tampa, FL 33613, USA.
authors.forename: Kirk P
authors.initials: KP
authors.lastname: Townsend
authors.forename: Martina
authors.initials: M
authors.lastname: Vendrame
authors.forename: Jared
authors.initials: J
authors.lastname: Ehrhart
authors.forename: Brandon
authors.initials: B
authors.lastname: Faza
authors.forename: Jin
authors.initials: J
authors.lastname: Zeng
authors.forename: Terrence
authors.initials: T
authors.lastname: Town
authors.forename: Jun
authors.initials: J
authors.lastname: Tan
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods*; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000906:Antibodies; D008070:Lipopolysaccharides; D020033:Protein Isoforms; D014409:Tumor Necrosis Factor-alpha; D017493:Leukocyte Common Antigens