Regulation of macrophage foam cell formation by αVβ3 integrin -: Potential role in human atherosclerosis
Regulation of macrophage foam cell formation by αVβ3 integrin -: Potential role in human atherosclerosis
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DOI：
10.1016/s0002-9440(10)63293-2
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发表时间：
2004-07-01
影响因子：
6
通讯作者：
Gerrity, RG
中科院分区：
文献类型：
--
作者：
Antonov, AS;Kolodgie, FD;Gerrity, RG
巨噬细胞泡沫细胞在动脉粥样硬化病变中的积累与该疾病的起始和进展均相关。清道夫受体CD36和SRA是负责将巨噬细胞转化为泡沫细胞的主要受体。整联蛋白alphavbeta3在分化几种细胞类型中起作用，但它参与了巨噬细胞的过渡。尚未检查进入泡沫细胞和该受体在动脉粥样硬化中的潜在作用。使用与alphavbeta3整合素特异性的固定单克隆抗体结合的单表面受体激活的体外模型，我们表明，alphavbeta3整合素的连接可通过通过CD36和SRA的CORECORCONCORDACTION下降到FOAM细胞表型中的血液单核细胞和巨噬细胞的分化。可以通过与内皮细胞接触来再现Alphavbeta3整联蛋白结扎的这种作用，而抑制alphavbeta3受体结扎仪可恢复氧化的低密度脂蛋白的摄取。此外，我们发现在巨噬细胞的原位很容易检测到alphavbeta3整合素。在早期和晚期动脉粥样硬化病变中，并且在体外暴露于氧化的低密度脂蛋白上上调α3整合素的表达。我们假设Alphavbeta3整联蛋白以持久的方式调节巨噬细胞的功能成熟到泡沫细胞中，因此，通过靶向alphavbeta3受体，可能有可能调节人类动脉粥样硬化的进展。
The accumulation of macrophage foam cells in atherosclerotic lesions is associated with both initiation and progression of this disease. Scavenger receptors CD36 and SRA are the primary receptors responsible for conversion of macrophages into foam cells. Integrin alphaVbeta3 plays a role in the differentiation of several cell types, but its involvement in the transition of macrophages; into foam cells and the potential role of this receptor in atherosclerosis have not been examined. Using an in vitro model of single surface receptor activation by binding with an immobilized monoclonal antibody specific to alphaVbeta3 integrin we show that ligation of alphaVbeta3 integrin prevents differentiation of blood monocytes and macrophages into the foam cell phenotype via coordinate down-regulation of CD36 and SRA. This effect of alphaVbeta3 integrin ligation can be reproduced by contact with endothelial cells, whereas the inhibition of alphaVbeta3 receptor ligation restores the uptake of oxidized low-density lipoprotein. Moreover, we found that alphaVbeta3 integrin is readily detected in situ on macrophages; in early and advanced atherosclerotic lesions and that in vitro exposure to oxidized low-density lipoprotein up-regulates alphaVbeta3 integrin expression. We hypothesize that alphaVbeta3 integrin regulates macrophage functional maturation into foam cells in a persistent manner, and therefore, by targeting alphaVbeta3 receptor it could potentially be possible to regulate progression of atherosclerosis in humans.