Inhibition of human activated Factor X by antithrombin III and alpha 1-proteinase inhibitor in human plasma.
The inhibition of activated human Factor X by human plasma protease inhibitors was investigated in both purified and plasma systems. In the former, antithrombin III, alpha 1-proteinase inhibitor, and alpha 2-macroglobulin, at normal plasma concentrations, markedly inhibited activated Factor X. Significant inhibition by alpha 2-antiplasmin, however, was only achieved when present at 40 times its plasma concentration. The relative rates of inhibition of activated Factor X coagulant activity in normal human plasma, antithrombin III-deficient plasma, and alpha 1-proteinase inhibitor-deficient plasma were 1.0, 0.63, and 0.75, respectively. From these relative rates of inhibition and their measured concentrations in the 3 plasmas, it was calculated that antithrombin III, alpha 1-proteinase inhibitor, and alpha 2-macroglobulin contribute 53, 35, and 12%, respectively, to the inhibition of activated Factor X in normal human plasma. Using 125I-labeled activated Factor X and a combination of sodium dodecyl sulfate disc gel electrophoresis and immunoadsorption, it was then demonstrated that antithrombin III accounted for 45-55%, alpha 1-proteinase inhibitor, 35-40%, and alpha 2-macroglobulin, 10-15% of the inhibition of the labeled protease in normal human plasma. The values obtained with the deficient plasmas are consistent with the distribution of activated Factor X-inhibitor complexes in normal human plasma. These data show by two independent techniques, one measuring coagulant activity and the other 125I-labeled activated Factor X-inhibitor complexes, that both antithrombin III and alpha 1-proteinase inhibitor are the major inhibitors of activated Factor X in normal human plasma.
D000990:Antithrombin III / Q000494:pharmacology*; D001798:Blood Proteins / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005170:Factor X / Q000037:antagonists & inhibitors*; D015951:Factor Xa; D006801:Humans; D007163:Immunosorbent Techniques; D000515:alpha 1-Antitrypsin; D000511:alpha-Macroglobulins / Q000494:pharmacology
D001798:Blood Proteins; D000515:alpha 1-Antitrypsin; D000511:alpha-Macroglobulins; D000990:Antithrombin III; D005170:Factor X; D015951:Factor Xa