Mechanisms of platelet response to monosodium urate crystals.
The mechanisms of urate-crystal-induced release of platelet constituents has been studied morphologically and biochemically. Urate crystals provoked an early energy-dependent release of the dense-body constituents serotonin, ADP, and ATP from washed platelets. Concurrently, platelet ultrastructure showed evidence of shape change, contractile wave, and aggregation. These are typical morphologic concomitants of platelet secretion. By 30 minutes' incubation, urate-induced platelet lysis occurred, as shown by loss of the cytoplasmic enzyme lactic dehydrogenase (LDH) and ultrastructurally by disruption of platelet membrane integrity. Cytochalasin B inhibited the urate-crystal-induced shape change, aggregation, and disruption of cell membranes. Platelet degranulation was not inhibited and the initial component of serotonin release was not affected. Cytochalasin B also abrogated crystal-induced LDH loss. Thus, the initial crystal-induced serotonin release does not depend on platelet lysis. It is concluded that urate-crystal--induced release of serotonin, ATP, and ADP represents an example of platelet secretion.