Human Blood-Derived Macrophages Induce Apoptosis in Human Plaque-Derived Vascular Smooth Muscle Cells by Fas-Ligand/Fas Interactions

摘要: Human atherosclerotic plaques that rupture are characterized by relatively low vascular smooth muscle cell (VSMC) and high inflammatory contents. Ruptured also contain higher numbers of apoptotic VSMCs than do stable lesions, suggesting VSMC apoptosis may promote plaque rupture. We examined the ability human monocytes/macrophages to induce derived from carotid plaque, aortic media, coronary media. Macrophages, but not T lymphocytes, induced a dose-dependent VSMCs, which required monocyte maturation macrophages direct cell-cell contact/proximity. was inhibited neutralizing antibodies Fas-ligand (Fas-L) or an Fas-Fc fusion protein, indicating requirement for membrane-bound Fas Fas-L. Monocyte associated with increased surface expression Fas-L, coincident onset cytotoxicity. expressed Fas, in underwent Fas-induced apoptosis. conclude potently apoptosis, requires interactions is part dependent on Fas/Fas-L interactions. Macrophage-induced therefore directly