High Molecular Weight Kininogen : Localization in the Unstimulated and Activated Platelet

High mol wt kininogen (HMWK), the major cofactorsubstrate of the contact phase of coagulation, is contained within and secreted by platelets. Studies have been performed to localize platelet HMWK in both the unstimulated and activated platelet and to ascertain the effect of platelet enzymes on HMWK itself. On platelet subcellular fractionation, platelet HMWK was localized to a-granules, and platelets from a patient with a deficiency of these granules (gray platelet syndrome) had 28% normal platelet HMWK. Platelet HMWK, in addition to being secreted from the platelet, was also localized to the surface of the platelet when activated. Using a competitive enzyme-linked immunosorbent assay for HMWK as an indirect antibody consumption assay, the external membrane of thrombinactivated platelets as well as the releasate from these stimulated platelets had 1 7 ng HMWK antigen! 1 0’ platelets available, whereas unstimulated platelets and their supernatant had only 4.9 and 4.2 ng HMWK/ 1 0’ platelets present. respectively. The anti-HMWK antibody consumption by activated normal platelets was specific for membrane-expressed platelet HMWK, since activated platelets from a patient with total kininogen deficiency did not