Modulation of heparin cofactor II activity by histidine-rich glycoprotein and platelet factor 4.
Modulation of heparin cofactor II activity by histidine-rich glycoprotein and platelet factor 4.
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富含组氨酸的糖蛋白和血小板因子 4 对肝素辅因子 II 活性的调节。
DOI：
10.1172/jci111725
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Pestka,CA
中科院分区：
文献类型：
--
作者：
Tollefsen,DM;Pestka,CA
肝素辅因子II是一种血浆蛋白，在肝素或硫酸皮肤素存在的情况下，它能迅速抑制凝血酶。我们已经确定了两种糖胺聚糖结合蛋白，即富含组氨酸的糖蛋白和血小板因子4对这些反应的影响。以13微克富组氨酸糖蛋白/微克肝素的比例纯化的富组氨酸糖蛋白可完全阻止肝素、辅因子II和肝素对凝血酶的抑制作用。相反，当富含组氨酸的糖蛋白/硫酸皮肤素的比例小于或等于128微克时，富含组氨酸的糖蛋白对肝素辅因子II和硫酸皮肤素对凝血酶的抑制作用没有影响。从血浆中去除85-90%的富含组氨酸的糖蛋白可以使延长凝血酶凝固时间所需的肝素量减少四倍，从14 S延长到180 S以上，但对类似抗凝作用所需的硫酸皮肤素的量没有影响。与富含组氨酸的糖蛋白相反，在肝素或硫酸皮肤素存在的情况下，纯化的血小板因子4阻止了肝素辅助因子II对凝血酶的抑制，比例为2微克血小板因子4/微克糖胺聚糖。此外，经花生四烯酸处理的血小板上清液可在肝素或硫酸皮肤素存在的情况下阻止肝素辅因子II对凝血酶的抑制。结论富含组氨酸的糖蛋白和血小板第4因子可以调节肝素辅因子II的抗凝血酶活性。
Heparin cofactor II is a plasma protein that inhibits thrombin rapidly in the presence of either heparin or dermatan sulfate. We have determined the effects of two glycosaminoglycan-binding proteins, i.e., histidine-rich glycoprotein and platelet factor 4, on these reactions. Inhibition of thrombin by heparin cofactor II and heparin was completely prevented by purified histidine-rich glycoprotein at the ratio of 13 micrograms histidine-rich glycoprotein/microgram heparin. In contrast, histidine-rich glycoprotein had no effect on inhibition of thrombin by heparin cofactor II and dermatan sulfate at ratios of less than or equal to 128 micrograms histidine-rich glycoprotein/microgram dermatan sulfate. Removal of 85-90% of the histidine-rich glycoprotein from plasma resulted in a fourfold reduction in the amount of heparin required to prolong the thrombin clotting time from 14 s to greater than 180 s but had no effect on the amount of dermatan sulfate required for similar anti-coagulant activity. In contrast to histidine-rich glycoprotein, purified platelet factor 4 prevented inhibition of thrombin by heparin cofactor II in the presence of either heparin or dermatan sulfate at the ratio of 2 micrograms platelet factor 4/micrograms glycosaminoglycan. Furthermore, the supernatant medium from platelets treated with arachidonic acid to cause secretion of platelet factor 4 prevented inhibition of thrombin by heparin cofactor II in the presence of heparin or dermatan sulfate. We conclude that histidine-rich glycoprotein and platelet factor 4 can regulate the antithrombin activity of heparin cofactor II.Images