Evidence for thrombin-induced human platelet secretion regulated by the cytoskeleton

Human blood platelets store an abundance of growth factors, adhensive proteins, coagulation factors, platelet-specific proteins, calcium, serotonin, and adenine nucleotides in their secretory organelles. After exposure to stimuli (thrombin, collagen, ADP, etc.), the platelets undergo a rapid series of morphological change from characteristic disks to spheres with several filopodia, adhension to the inner surface of blood vessels, and aggregation among the platelets. Most of these changes are usually accompanied by secretion or release of dense bodies (release I) and alpha-granules (release II). The secreted products play essential parts in a variety of important physiological and/or pathological events, such as hematosis, thrombosis, blood coagulation, inflammation, and atherosclerosis. Little is known, however, for regulatory mechanism of platelet secretion. Platelets are a distinct kind of cells with many special organelles, but without a nucleus. It also contains a large amount of cytoskeleton. The numerous investigators have suggested that the platelet responses to stimuli are intimately linked to events involving cytoskeleton within the platelets. During platelet activation, as revealed by electron microscopy, the secretory organelles become centralized and enveloped by circular microtubules and a filamentous network. It is implied a possible relationship between cytoskeleton and platelet secretion. However, the precise role of cytoskeleton in platelet secretion remains uncertain. By using exposed GMP-140 (a platelet granule-membrane protein with MW of 140 kDa) as a specific signal of secretion, the present study was designed to investigate the effects of microtubular and microfilamental inhibitors on thrombin-induced platelet secretion.