Cytofluorometric identification of plasmin-sensitive factor XIIIa binding to platelets.
We have investigated the binding of blood coagulation factor XIIIa to thrombin-stimulated platelets using cytofluorometric analysis. Washed thrombin-stimulated platelets bound exogenously added factor XIIIa in a calcium-dependent reaction. The expression of endogenous platelet factor XIII was also detected on the surface of thrombin-stimulated platelets. When fluorescence analysis was performed based on particle size, factor XIIIa bound to the surface of greater than 95% of particles which contained more than one platelet, but only 50% of single platelets. The binding of factor XIIIa to thrombin-stimulated platelets was inhibited by plasmin. Plasmin also inhibited thrombin-dependent expression of the factor XIIIa binding site on platelets. Experiments in which thrombin-stimulated platelets were incubated with factor XIIIa in the presence of 125I-dimethylcasein or 3H-putrescine demonstrated that platelets bear both glutamyl and lysyl substrates for factor XIIIa. Thrombin increased the expression of factor XIIIa substrates by platelets. Plasmin inhibited both the expression of factor XIIIa substrates and degraded them. The binding of factor XIIIa to thrombin-stimulated platelets and the availability of factor XIIIa substrates on the platelet surface could provide a mechanism by which factor XIIIa stabilizes the hemostatic plug by promoting crosslinking reactions between platelet membrane proteins and adhesive glycoproteins. In contrast, plasmin inhibition of factor XIIIa binding and crosslinking could disrupt hemostasis.
D001792:Blood Platelets / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005176:Factor XIII / Q000378:metabolism*; D005341:Fibrinolysin / Q000502:physiology; D005434:Flow Cytometry; D005971:Glutamates / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008239:Lysine / Q000378:metabolism; D011503:Transglutaminases
D005971:Glutamates; D005176:Factor XIII; D011503:Transglutaminases; D005341:Fibrinolysin; D008239:Lysine