Antithrombin action of phosvitin and other phosphate-containing polyanions is mediated by heparin cofactor II.
We have examined the antithrombin effects of various phosphate-containing polyanions (including linear polyphosphates, polynucleotides and the phosphoserine glycoprotein, phosvitin) on the glycosaminoglycan-binding plasma proteinase inhibitors, antithrombin III (ATIII) and heparin cofactor II (HCII). These phosphate-containing polyanions accelerate the HCII-thrombin reaction, as much as 1600-fold in the case of phosvitin. The HCII-thrombin reaction with both phosvitin and polynucleotides appears to follow the ternary complex mechanism. The HCII-thrombin complex is rapidly formed in the presence of these phosphate polyanions (each at 10 micrograms/ml) when 125I-labeled thrombin is incubated with human plasma (ex vivo). None of these phosphate polyanions accelerate the ATIII-thrombin reaction. Our results suggest that the antithrombotic effect of these phosphate-containing polyanions is mediated by HCII activation and not by ATIII.
Church
F C
FC
Center for Thrombosis and Hemostasis, University of North Carolina School of Medicine, Chapel Hill 27599.
Pratt
C W
CW
Treanor
R E
RE
Whinna
H C
HC
D000990:Antithrombin III / Q000502:physiology; D000991:Antithrombins / Q000502:physiology*; D004527:Egg Proteins / Q000494:pharmacology*; D006023:Glycoproteins / Q000502:physiology*; D015844:Heparin Cofactor II; D006801:Humans; D007700:Kinetics; D010774:Phosvitin / Q000494:pharmacology*; D011131:Polyribonucleotides / Q000494:pharmacology*; D013917:Thrombin / Q000378:metabolism
D000991:Antithrombins; D004527:Egg Proteins; D006023:Glycoproteins; D011131:Polyribonucleotides; D015844:Heparin Cofactor II; D000990:Antithrombin III; D010774:Phosvitin; D013917:Thrombin