Title: DETECTION AND EFFECTS OF THROMBOMODULIN ACTIVITY IN CRUDE THROMBOPLASTIN PREPARATIONS FROM PLACENTA AND LUNG
Abstract: The activation of protein C (PC) by thrombin requires the presence of an endothelial membrane cofactor, thrombomodulin (TM). Activated PC (APC) exerts its anticoagulant activity by degrading factors (F) Va and Villa in the presence of phospholipids and of a vitamin K-dependent cofactor, protein S. Tissue factor (TF) is the essential cofactor of factor Vll/VIIain the activation of factor X. TF is synthetized by several cell lines including endothelial cells. Using a specific TM assay, up to 0.85 units of TM activity could be detected in commercial thromboplastin (TP) preparations from human placenta or rabbit or porcine lung, when the amount of TP was adjusted to contain 1 unit of TF activity. Preparations from brain contained very low amounts, if any, of this activity (< 0.02 TM units). In order to evaluate the effects of the presence of TM activity in some TP preparations, the stability of F V and VIII activities was examined after activation of the coagulation system by these TP in various plasmas. PC deficient plasmas, plasmas lacking F V, VIII or IX and immunoadsorbed PC deficient plasma supplemented with purified human PC (5 Ug/ml) were used. After activation with placenta or lung TP, F V and VIII activities were markedly reduced ( ∼ 90 % reduction) in normal and hemophiliac plasmas, whereas they remained high after activation with brain TP. F V and VIII activities were preserved in protein C deficient plasma after activation by all TP preparations. The same decrease of F V and VIII activities was observed after activation of immunoadsorbed PC deficient plasma supplemented with purified PC with placenta or lung TP only. Preincubation of TP from human placenta with antibodies to human TM raised in laying hens abolished the capacity of this preparation to destroy F V activity of PC containing plasmas. These results establish the presence of TM activity in crude thromboplastin preparations from placenta or from lung. Surprisingly, this anti-coagulant activity seems to be absent from brain. TM from placenta or lung extracts is responsible for the degradation of F V and VIII.
Publication Year: 1987
Publication Date: 1987-01-01
Language: en
Type: article
Indexed In: ['crossref']
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