EXPRESSION OF CD54 (INTERCELLULAR-ADHESION MOLECULE-1) AND THE BETA-1INTEGRIN CD29 IS MODULATED BY A CYCLIC-AMP-DEPENDENT PATHWAY IN ACTIVATED PRIMARY RAT MICROGLIAL CELL-CULTURES

Microglial cell activation plays a central role in acute and chronic i nflammatory 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 inter feron, IFN gamma, exhibited a 2-3 fold increase in CD54 expression, an increase in CD29 and no change in CD11b. Maximal increases in CD54 an d CD29 staining on CD11b positive microglial cells were apparent 20-24 h after LPS and IFN gamma while nitrite production reflecting inducib le nitric oxide synthase activity, continued to increase. The increase s in CD29 and CD54 staining were inhibited in a dose dependent manner by agents which increased intracellular cAMP levels including 100 mu M 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. Concomi tant with the dose dependent decreases in CD29 and CD54 staining were increases in intracellular cAMP and reduced TNF secretion. These resul ts suggest that regulation of CD29 and CD54 expression on activated mi croglial cells involves a cAMP dependent pathway.