Human blood-derived macrophages induce apoptosis in human plaque-derived vascular smooth muscle cells by Fass-ligand/Fas interactions
Human blood-derived macrophages induce apoptosis in human plaque-derived vascular smooth muscle cells by Fass-ligand/Fas interactions
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DOI：
10.1161/hq0901.094279
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发表时间：
2001-09-01
影响因子：
8.7
通讯作者：
Bennett, MR
中科院分区：
文献类型：
--
作者：
Boyle, JJ;Bowyer, DE;Bennett, MR
人类动脉粥样硬化斑块破裂的特征是相对低的血管平滑肌细胞（VSMC）和高的炎性细胞含量。破裂斑块中凋亡的VSMC数量也高于稳定斑块，提示VSMC凋亡可能促进斑块破裂。我们检测了人单核细胞/巨噬细胞诱导人颈动脉斑块、主动脉中膜和冠状动脉中膜来源的VSMC凋亡的能力。巨噬细胞，而不是T淋巴细胞，诱导VSMC的剂量依赖性凋亡，这需要单核细胞成熟为巨噬细胞和直接的细胞-细胞接触/接近。抗Fas配体（Fas-L）中和抗体或Fas-Fc融合蛋白可抑制VSMC凋亡，表明需要膜结合Fas和Fas-L。单核细胞成熟与Fas-L的表面表达增加相关，与细胞毒性的发生一致。VSMCs表达表面Fas，斑块VSMCs表达增加，斑块VSMCs也发生Fas诱导的凋亡。我们的结论是，人巨噬细胞有效地诱导人VSMC凋亡，这需要直接的细胞-细胞相互作用，部分依赖于Fas/Fas-L相互作用。因此，巨噬细胞诱导的VSMC凋亡可能直接促进斑块破裂。
Human atherosclerotic plaques that rupture are characterized by relatively low vascular smooth muscle cell (VSMC) and high inflammatory cell contents. Ruptured plaques also contain higher numbers of apoptotic VSMCs than do stable lesions, suggesting that VSMC apoptosis may promote plaque rupture. We examined the ability of human monocytes/macrophages to induce apoptosis of VSMCs derived from human carotid plaque, aortic media, and coronary media. Macrophages, but not T lymphocytes, induced a dose-dependent apoptosis of VSMCs, which required monocyte maturation to macrophages and direct cell-cell contact/proximity. VSMC apoptosis was inhibited by neutralizing antibodies to Fas-ligand (Fas-L) or an Fas-Fc fusion protein, indicating the requirement for membrane-bound Fas and Fas-L. Monocyte maturation was associated with increased surface expression of Fas-L, coincident with the onset of cytotoxicity. VSMCs expressed surface Fas, which was increased in plaque VSMCs, and plaque VSMCs also underwent Fas-induced apoptosis. We conclude that human macrophages potently induce human VSMC apoptosis, which requires direct cell-cell interactions and is in part dependent on Fas/Fas-L interactions. Macrophage-induced VSMC apoptosis may therefore directly promote plaque rupture.