CD45 isoform RB as a molecular target to oppose lipopolysaccharide-induced microglial activation in mice.
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.
Townsend
Kirk P
KP
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.
Vendrame
Martina
M
Ehrhart
Jared
J
Faza
Brandon
B
Zeng
Jin
J
Town
Terrence
T
Tan
Jun
J
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
D000906:Antibodies; D008070:Lipopolysaccharides; D020033:Protein Isoforms; D014409:Tumor Necrosis Factor-alpha; D017493:Leukocyte Common Antigens