Reduced uptake of plasminogen activators during formation of whole blood thrombi by a bovine polypeptide of uterine origin: in vitro study using Chandler's loop method

The authors have previously isolated and purified by high performance liquid chromatography low molecular weight polypeptide of uterine origin (LMW-UDF) which promotes metastasis in tumor-bearing mice. In order to determine what effects this polypeptide could have on the coagulation systems they generated whole blood thrombi in vitro in the presence (1 μg/ml - 100 μg/ml) or absence of test protein. Using trace amount of radiolabeled plasminogen activators, 125I-Urokinase and 125I-pro-Urokinase (single chain urokinase) inhibition of uptake to the thrombi was observed vs control groups. Also, specific radioactivity of the thrombi pre-incubated with LMW-UDF was statistically significantly lower than control thrombi (p < 0.001). Experiments with 125I-fibrinogen revealed no net increase or decrease of the uptake into the thrombi when LMW-UDF was used. Gross morphological differences were noted in the group with 1 μg/ml LMW-UDF, where weight was significantly greater (243.56 mg +/- SD 50.44) and size was significantly larger (3.5 cm +/- SD 0.6) when compared to the control groups (61.45 mg +/- SD 10.26 and 0.8 cm +/- SD 0.3), respectively. It appears that LMW-UDF has an influence on the physical formation of whole blood thrombi and suggests that this effect is mediated possibly by the uptake of Urokinase and pro-Urokinase. The actual mechanism of the action is unknown but may be caused by altered fibrin cross-linking or platelet aggregation