| To study interactions between platelets and the fibrinolytic system,
we examined the effects of human plasmin on human platelets washed by
gel filtration. Plasmin concentrations that did not affect platelet
shape change, release, or aggregation (less than 1.0 caseinolytic
units [CU]/ml) caused a dose- and time-dependent inhibition of
platelet aggregation in response to thrombin, ionophore A23187, and
collagen. Complete loss of aggregation occurred at 0.1-0.5 CU/ml of
plasmin. In a parallel dose-dependent manner, plasmin likewise
inhibited thrombin, ionophore, and collagen-stimulated thromboxane B2
production. In contrast, neither aggregation nor thromboxane B2
formation induced by arachidonate was inhibited by plasmin
pretreatment of the platelets. Plasmin blocked the thrombin-induced
release of [3H]arachidonic acid from platelet membrane phospholipids
and the thrombin-induced platelet oxygen burst. However, plasmin did
not inhibit the arachidonate-induced oxygen burst. Inhibition of
arachidonic acid release by plasmin was not mediated by increase in
platelet cyclic AMP. These results suggest that plasmin inhibits
platelet function, at least in part, by blocking the mobilization of
arachidonic acid from membrane phospholipid pools. The effects of
plasmin on platelets may contribute to the hemostatic abnormalities
seen in pathologic and pharmacologic fibrinolysis.
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