Leukocytes, when exposed to activating stimuli, are capable of a wide variety of responses that are important in coagulation events. The interactions of these cells with other blood components such as proteins, blood factors, and platelets affect the amount of thrombus formation that occurs after damage to the vascular system. The biomaterial-blood interaction also initiates a series of coagulation events that result in artificial surface-induced thrombosis. Although extensive research has been done to determine the role of platelets and proteins in thrombus formation and embolization, there has been only limited study of how leukocytes modulate these responses. We propose to investigate the role of peripheral blood leukocytes in blood-material interactions in vitro by exposing the cells te biomaterials which have markedly different surface properties. The leukocyte responses of adherence, phagocytosis, degranulation, and expression of procoagulant and fibrinolytic activity will be assessed. In addition, the activation of complement by biomaterials, and subsequent leukocyte aggregation will be investigated. In parallel experiments, plasma proteins which have been shown to be relevant to biomaterial thrombogenicity will be preadsorbed onto the polymer surfaces before exposure to leukocytes to examine their effect on the leukocyte response. Leukocyte interactions with platelets as a result of arachidonic acid metabolism will be investigated to determine the role of this metabolite in the cellular enhancement of thrombogenesis. Canine ex vivo experiments will provide information about the acute and chronic reaction of leukocytes to implantation of a polymer material through measurement of leukocyte deposition and morphology. These studies of leukocyte responses and thrombus formation will lead to a better understanding of the mechanisms involved in artificial surface-induced thrombogenesis and will aid in the design of improved biocompatible polymeric materials.
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