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, athero- sclerotic lesion stability, and clearance of aged cells by phago- cytosis. 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 thioglycol- late-elicited mouse peritoneal macrophages with various un- related apoptotic agents, including simvastatin, camptothe- cin, 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 mea- sured by changes in cell morphology, annexin V-labeling, and DNA fragmentation. We demonstrate that caveolin-1 in mac- rophages is present in lipid rafts and colocalizes with phos- phatidylserine (PS) at the cell surface of apoptotic macro- phages. Our data suggest that caveolin-1 increase is an early event, closely accompanied by PS externalization and inde- pendent of caspase activation and nuclear DNA fragmenta- tion. 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 apop- totic cells. —Gargalovic, P., and L. Dory. Cellular apoptosis is associated with increased caveolin-1 expression in macro- phages. J. Lipid Res. 2003. 44: 1622-1632.