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Journal of Lipid Research, Vol. 44, 1622-1632, September 2003
Copyright © 2003 by American Society for Biochemistry and Molecular Biology
Cellular apoptosis is associated with increased caveolin-1 expression in macrophages
Department of Molecular Biology & Immunology, The University of North Texas Health Science Center at Fort Worth, TX 76107
1 To whom correspondence should be addressed. e-mail: ldory{at}hsc.unt.edu
Macrophage apoptosis is an important factor in determining the efficiency of the immune response, atherosclerotic lesion stability, and clearance of aged cells by phagocytosis. The involvement of caveolin-1 in the regulation of apoptosis has been previously suggested in fibroblasts and epithelial cells. Here we show that treatment of thioglycollate-elicited mouse peritoneal macrophages with various unrelated apoptotic agents, including simvastatin, camptothecin, or glucose deprivation, is associated with a specific and large increase in caveolin-1 expression. In contrast, caveolin-2 levels remain unaffected. Induction of apoptosis was measured by changes in cell morphology, annexin V-labeling, and DNA fragmentation. We demonstrate that caveolin-1 in macrophages is present in lipid rafts and colocalizes with phosphatidylserine (PS) at the cell surface of apoptotic macrophages. Our data suggest that caveolin-1 increase is an early event, closely accompanied by PS externalization and independent of caspase activation and nuclear DNA fragmentation. The increase in caveolin-1 levels does not require new protein synthesis, as cycloheximide does not prevent the apoptosis-mediated increase in caveolin-1 levels. We propose that increased levels of caveolin-1 characterize the apoptotic phenotype of macrophages.
Caveolin-1 may be involved in the efficient externalization of PS at the surface of the apoptotic cells.
Abbreviations: PS, phosphatidylserine; PVDF, polyvinylidene fluoride; tg-MPM, thioglycollate-elicited mouse peritoneal macrophage
Supplementary key words caveolae • lipid raft • membrane phospholipids • phosphatidylserine • mouse
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