Expression of CD54 (Intercellular Adhesion Molecule-1) and the [beta]1 Integrin CD29 Is Modulated by a Cyclic AMP Dependent Pathway in Activated Primary Rat Microglial Cell Cultures

Byline: Steven H. Zuckerman (1), Jason Gustin (2), Glenn F. Evans (1) Abstract: Microglial cell activation plays a central role in acute and chronic inflammatory processes associated with neurodegeneration. As macrophage activation is generally associated with the up-regulation of specific surface antigens, the expression of CD54, and CD29 were evaluated on CD11b positive neonatal rat microglial cell cultures by flow cytometry. These cells when exposed to lipopolysaccharide, LPS, and gamma interferon, IFNI3, exhibited a 2--3 fold increase in CD54 expression, an increase in CD29 and no change in CD11b. Maximal increases in CD54 and CD29 staining on CD11b positive microglial cells were apparent 20--24 h after LPS and IFNI3 while nitrite production reflecting inducible nitric oxide synthase activity, continued to increase. The increases in CD29 and CD54 staining were inhibited in a dose dependent manner by agents which increased intracellular cAMP levels including 100 uM 8-bromoadenosine 3 :5 -cyclic monophosphate but not 8-bromoadenosine monophosphate, the phosphodiesterase inhibitor isobutyl methylxanthine and by direct activation of adenylate cyclase with forskolin. Concomitant with the dose dependent decreases in CD29 and CD54 staining were increases in intracellular cAMP and reduced TNF secretion. These results suggest that regulation of CD29 and CD54 expression on activated microglial cells involves a cAMP dependent pathway. Author Affiliation: (1) Division of Cardiovascular Research, Lilly Research Labs, Indianapolis, Indiana, 46285 (2) Department of Biology, DePauw University, Greencastle, Indiana Article History: Registration Date: 03/10/2004