CD45 isoform RB as a molecular target to oppose lipopolysaccharide-induced microglial activation in mice.
Publication/Presentation Date
5-13-2004
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.
Volume
362
Issue
1
First Page
26
Last Page
30
ISSN
0304-3940
Published In/Presented At
Townsend, K. P., Vendrame, M., Ehrhart, J., Faza, B., Zeng, J., Town, T., & Tan, J. (2004). CD45 isoform RB as a molecular target to oppose lipopolysaccharide-induced microglial activation in mice. Neuroscience letters, 362(1), 26–30. https://doi.org/10.1016/j.neulet.2004.01.082
Disciplines
Medicine and Health Sciences
PubMedID
15147773
Department(s)
Department of Medicine
Document Type
Article