Modulation of heparin cofactor II activity by histidine-rich glycoprotein and platelet factor 4.
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.
D001777:Blood Coagulation / Q000187:drug effects; D003871:Dermatan Sulfate / Q000494:pharmacology; D006023:Glycoproteins / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology; D015844:Heparin Cofactor II; D006801:Humans; D066298:In Vitro Techniques; D010978:Platelet Factor 4 / Q000502:physiology*; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology*; D000099053:Histidine-Rich Glycoprotein
D006023:Glycoproteins; D011506:Proteins; D000099053:Histidine-Rich Glycoprotein; D003871:Dermatan Sulfate; D010978:Platelet Factor 4; D015844:Heparin Cofactor II; D006493:Heparin