Gargalovic Peter, Dory Ladislav
Department of Molecular Biology & Immunology, The University of North Texas Health Science Center at Fort Worth, TX 76107, USA.
J Lipid Res. 2003 Sep;44(9):1622-32. doi: 10.1194/jlr.M300140-JLR200. Epub 2003 Jun 1.
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.
巨噬细胞凋亡是决定免疫反应效率、动脉粥样硬化病变稳定性以及通过吞噬作用清除衰老细胞的一个重要因素。此前已有研究表明，小窝蛋白-1在成纤维细胞和上皮细胞的凋亡调控中发挥作用。在此，我们发现，用包括辛伐他汀、喜树碱或葡萄糖剥夺在内的多种不相关凋亡剂处理巯基乙酸诱导的小鼠腹腔巨噬细胞，会导致小窝蛋白-1表达特异性大幅增加。相比之下，小窝蛋白-2水平则不受影响。通过细胞形态变化、膜联蛋白V标记和DNA片段化来检测凋亡的诱导情况。我们证明，巨噬细胞中的小窝蛋白-1存在于脂筏中，并在凋亡巨噬细胞的细胞表面与磷脂酰丝氨酸（PS）共定位。我们的数据表明，小窝蛋白-1的增加是一个早期事件，与PS外化密切相关，且独立于半胱天冬酶激活和核DNA片段化。小窝蛋白-1水平的增加不需要新的蛋白质合成，因为放线菌酮并不能阻止凋亡介导的小窝蛋白-1水平增加。我们提出，小窝蛋白-1水平的升高是巨噬细胞凋亡表型的特征。小窝蛋白-1可能参与凋亡细胞表面PS的有效外化。
