Cellular apoptosis is associated with increased caveolin-1 expression in macrophages.
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.
Gargalovic
Peter
P
Department of Molecular Biology & Immunology, The University of North Texas Health Science Center at Fort Worth, TX 76107, USA.
Dory
Ladislav
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D051242:Caveolin 1; D051243:Caveolin 2; D022461:Caveolins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism; D051379:Mice; D014176:Protein Biosynthesis; D019821:Simvastatin / Q000494:pharmacology; D015854:Up-Regulation
C495541:Cav1 protein, mouse; D051242:Caveolin 1; D051243:Caveolin 2; D022461:Caveolins; D019821:Simvastatin; D020169:Caspases