Arachidonic acid and stable analogue of prostaglandin endoperoxides (U46619) induce platelet spreading and thrombi-like aggregate formation on a collagen substrate. Effect of fluid dynamics

Soluble plasma inducers and inhibitors of platelet activity and fluid dynamics of the blood stream are effective modulators of platelet-vessel wall interactions. Effects of platelet activity inducers, arachidonic acid (AA) and stable prostaglandin endoperoxides analogue (U46619), on platelet disposition on the bottom of multiwell tissue culture plates coated with fibrillar calf skin collagen (CSC) have been studied by scanning electron microscopy (SEM). Both agents stimulate platelet spreading and formation of large surface-bound multilayer (thrombi-like) aggregates on a CSC substrate. AA and U46619 effects on spreading and thrombi-like aggregate formation depend on the speed of platelet suspension shaking during platelet deposition on the surface. In the absence of shaking, both inducers mainly stimulate the spreading of platelets: spread platelets fuse and form widespread sheets covering up to 50% of the CSC-coated surface. An increase in the shaking speed leads to the decrease of the platelet spreading, while the number of surface-bound thrombi-like aggregates grows, reaching the maximum at a shaking speed of 40 back and forth cycles per min. The thrombi-like aggregates mainly consist of fused platelets and always contain the basal sheet of spread platelets, which suggests the participation of the latter in aggregate attachment to the surface. Large aggregates are absent in the population of nonadherent platelets. The obtained data indicate that AA metabolites participate in platelet spreading and thrombi-like aggregate formation, the processes specific for platelet-surface interactions. The use of the suggested model for the in vitro study of platelet spreading and mural thrombi formation, and for screening of antithrombotic and thrombolytic drugs is discussed.