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Investigation of a thrombin-complexing protein associated with platelets

Thesis/Dissertation ·
OSTI ID:7105715
A fraction of the {sup 125}I-thrombin that binds to human platelets is taken into a sodium dodecyl sulfate-resistant 77k Da complex with a platelet factor. This platelet factor is in several respects similar to protease nexin I (PNI), a fibroblasts thrombin inhibitor. The complexes are of the right size, bind to agarose that has been derivatized with either anti-PNI antibody or heparin, do not form when the thrombin active site has been blocked with diisopropylphosphofluoridate, and do not appear on platelets when heparin is present. The interaction with the platelet surface may modulate the conformation and function of this platelet form of protease nexin I (PNI{sub p}) because: (i) an antibody against protease nexi I inhibited released PNI{sub p}, but not platelet-bound PNI{sub p} from complexing {sup 125}I-thrombin, and (ii) whereas PNI{sub p} extracted from platelets bound both thrombin and urokinase, platelet-bound PNI{sub p} bound only thrombin. In experiments employing several different platelet isolation methods, PNI{sub p} accounted for a large fraction of the rapid high affinity binding of {sup 125}I-thrombin to platelets. However, platelets isolated and maintained in the presence of metabolic inhibitors failed to take added thrombin into {sup 125}I-thrombine-PNI{sub p} complexes.
Research Organization:
Kansas Univ., Lawrence, KS (USA)
OSTI ID:
7105715
Country of Publication:
United States
Language:
English