Human thrombomodulin is not an efficient inhibitor of the procoagulant activity of thrombin.
The effect of human thrombomodulin isolated from placenta on the procoagulant activity of thrombin was studied and compared to that of rabbit thrombomodulin. The isolated protein was proved to be thrombomodulin because a rabbit antibody against the isolated protein blocked protein C activation by thrombomodulin in solution and also blocked the protein-C-activating cofactor activity of human umbilical vein endothelial cells. The affinity of human thrombomodulin for human thrombin in the presence of fibrinogen is 30 times less than that of rabbit thrombomodulin. This value is based on the measurements of the clotting time of human fibrinogen and thrombin in the presence of increasing amounts of thrombomodulin. Human thrombomodulin was also much less effective compared with rabbit thrombomodulin in inhibiting thrombin-induced human coagulation factor V activation. The ability to inhibit release of [3H]serotonin from washed human platelets was at least 10 times less using human thrombomodulin compared with rabbit thrombomodulin. A partially purified preparation of human lung thrombomodulin was also relatively ineffective in inhibiting thrombin-induced serotonin release from platelets, indicating that the difference between rabbit and human thrombomodulin is one of species rather than of tissue. Thus, while human thrombomodulin is a potent cofactor in protein C activation, it is not an efficient inhibitor of the procoagulant actions of thrombin.
Maruyama
I
I
Salem
H H
HH
Ishii
H
H
Majerus
P W
PW
D000328:Adult; D000818:Animals; D001777:Blood Coagulation; D001792:Blood Platelets / Q000378:metabolism; D005165:Factor V / Q000096:biosynthesis; D015943:Factor Va; D005340:Fibrinogen / Q000502:physiology; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D008168:Lung / Q000378:metabolism; D008297:Male; D011486:Protein C; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000276:immunology / Q000502:physiology*; D018179:Receptors, Thrombin; D012701:Serotonin / Q000097:blood; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D006023:Glycoproteins; D007106:Immune Sera; D011486:Protein C; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin; D012701:Serotonin; D015943:Factor Va; D005165:Factor V; D005340:Fibrinogen; D013917:Thrombin