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Expression of CD54 (intercellular adhesion molecule-1) and the beta 1 integrin CD29 is modulated by a cyclic AMP
S H Zuckerman1, J Gustin, G F Evans
1Division of Cardiovascular Research, Lilly Research Labs, Indianapolis, Indiana 46285, USA.
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, IFN gamma, 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 IFN gamma 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 microM 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.
Insights
Microglial activation in neurodegeneration involves changes in cell surface proteins. Cyclic AMP (cAMP) signaling pathways regulate these changes, impacting inflammatory responses in the brain.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglial cell activation is crucial in neurodegenerative diseases.
- Macrophage activation typically involves up-regulation of surface antigens.
Purpose of the Study:
- To investigate the expression of CD54 and CD29 on activated microglial cells.
- To explore the role of cyclic AMP (cAMP) in regulating these microglial responses.
Main Methods:
- Flow cytometry was used to analyze CD54 and CD29 expression on neonatal rat microglial cultures.
- Cells were stimulated with lipopolysaccharide (LPS) and interferon-gamma (IFN-γ).
- The effects of cAMP-elevating agents and phosphodiesterase inhibitors were assessed.
Main Results:
- LPS and IFN-γ stimulation significantly increased CD54 and CD29 expression on CD11b-positive microglial cells.
- Nitrite production, indicative of inducible nitric oxide synthase activity, continued to rise.
- Increased intracellular cAMP levels, induced by agents like 8-bromoadenosine 3':5'-cyclic monophosphate, forskolin, and isobutyl methylxanthine, inhibited CD54 and CD29 expression.
- These cAMP-mediated effects were associated with reduced TNF secretion.
Conclusions:
- Microglial cell activation involves the modulation of CD54 and CD29 surface markers.
- A cAMP-dependent pathway plays a significant role in regulating CD54 and CD29 expression on activated microglial cells.
- These findings offer insights into potential therapeutic targets for neuroinflammatory conditions.