Formation of protease nexin-thrombin complexes on the platelet surface.
We have recently described a platelet factor that is similar to the fibroblast thrombin inhibitor protease nexin I (PNI). The present manuscript shows that this platelet form of PN (PNp) does not complex [125I]-thrombin that has been blocked at its active site, consistent with the conclusion that it is a thrombin inhibitor. When platelets are incubated with [125I]-thrombin, PNp-[125I]-thrombin complexers accumulate both in the medium and on the platelet surface. In the case of fibroblasts, PNI-[125I]-thrombin complexes that form in solution bind to the cells as a consequence of a receptor-mediated clearance process [Low et al, Proc Natl Acad Sci USA 78:2340, 1981]. We show here that the PNp-[125I]-thrombin complexes that accumulate in platelet-binding incubation medium do not bind to platelets. Thus, the platelet-associated complexes must form by [125I]-thrombin binding to PNp that is associated with the platelet surface. Pretreatment of platelets with heparin markedly increases the number of PNp-[125I]-thrombin complexes that form on platelets. The basis for this increase is unclear. This effect seems incompatible with a heparinlike factor acting as the surface binding site for PNp.
D016564:Amyloid beta-Protein Precursor; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002352:Carrier Proteins / Q000097:blood*; D006493:Heparin / Q000494:pharmacology; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D013917:Thrombin / Q000378:metabolism*
D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D006629:Hirudins; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D006493:Heparin; D013917:Thrombin