CD36 mediates the In vitro inhibitory effects of thrombospondin-1 on endothelial cells.
CD36 mediates the In vitro inhibitory effects of thrombospondin-1 on endothelial cells.
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DOI：
10.1083/jcb.138.3.707
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发表时间：
1997-08-11
期刊：
影响因子：
--
通讯作者：
Bouck NP
中科院分区：
文献类型：
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作者：
Dawson DW;Pearce SF;Zhong R;Silverstein RL;Frazier WA;Bouck NP
血小板反应蛋白-1（TSP-1）是一种天然存在的血管生成抑制剂，能够使正常内皮细胞对多种诱导剂无反应。在这里，我们使用天然TSP-1和小的抗血管生成肽从它表明，这种抑制作用是由CD 36，微血管内皮细胞上发现的跨膜糖蛋白介导的。抗CD 36和谷胱甘肽-S-转移酶-CD 36融合蛋白（包含TSP-1结合位点）的IgG抗体均阻断完整TSP-1及其活性肽抑制培养的微血管内皮细胞迁移的能力。此外，抗血管生成TSP-1肽抑制天然TSP-1与固相CD 36及其融合蛋白以及与表达CD 36的细胞的结合。已知结合CD 36的其他分子，包括IgM抗CD 36抗体SM β、氧化（但非未氧化）低密度脂蛋白和人胶原蛋白1，通过抑制人微血管内皮细胞的迁移模拟TSP-1。用CD 36表达质粒转染CD 36缺陷的人脐静脉内皮细胞，使其对TSP-1抑制其迁移和管形成变得敏感。这项工作表明，内皮CD 36，以前被认为是参与粘附和清除活动，可能是必不可少的抑制血管生成的血小板反应蛋白-1。
Thrombospondin-1 (TSP-1) is a naturally occurring inhibitor of angiogenesis that is able to make normal endothelial cells unresponsive to a wide variety of inducers. Here we use both native TSP-1 and small antiangiogenic peptides derived from it to show that this inhibition is mediated by CD36, a transmembrane glycoprotein found on microvascular endothelial cells. Both IgG antibodies against CD36 and glutathione-S-transferase–CD36 fusion proteins that contain the TSP-1 binding site blocked the ability of intact TSP-1 and its active peptides to inhibit the migration of cultured microvascular endothelial cells. In addition, antiangiogenic TSP-1 peptides inhibited the binding of native TSP-1 to solid phase CD36 and its fusion proteins, as well as to CD36-expressing cells. Additional molecules known to bind CD36, including the IgM anti-CD36 antibody SM∅, oxidized (but not unoxidized) low density lipoprotein, and human collagen 1, mimicked TSP-1 by inhibiting the migration of human microvascular endothelial cells. Transfection of CD36-deficient human umbilical vein endothelial cells with a CD36 expression plasmid caused them to become sensitive to TSP-1 inhibition of their migration and tube formation. This work demonstrates that endothelial CD36, previously thought to be involved only in adhesion and scavenging activities, may be essential for the inhibition of angiogenesis by thrombospondin-1.