title: Intravascular filarial parasites inhibit platelet aggregation. Role of parasite-derived prostanoids.
abstract: The nematode parasites that cause human lymphatic filariasis survive for long periods in their vascular habitats despite continual exposure to host cells. Platelets do not adhere to blood-borne microfilariae, and thrombo-occlusive phenomena are not observed in patients with circulating microfilariae. We studied the ability of microfilariae to inhibit human platelet aggregation in vitro. Brugia malayi microfilariae incubated with human platelets caused dose-dependent inhibition of agonist-induced platelet aggregation, thromboxane generation, and serotonin release. As few as one microfilaria per 10(4) platelets completely inhibited aggregation of platelets induced by thrombin, collagen, arachidonic acid, or ionophore A23187. Microfilariae also inhibited aggregation of platelets in platelet-rich plasma stimulated by ADP, compound U46619, or platelet-activating factor. The inhibition required intimate proximity but not direct contact between parasites and platelets, and was mediated by parasite-derived soluble factors of low (less than 1,000 Mr) molecular weight that were labile in aqueous media and caused an elevation of platelet cAMP. Prior treatment of microfilariae with pharmacologic inhibitors of cyclooxygenase decreased both parasite release of prostacyclin and PGE2 and microfilarial inhibition of platelet aggregation. These results indicate that microfilariae inhibit platelet aggregation, via mechanisms that may include the elaboration of anti-aggregatory eicosanoids.
authors.affiliation: Charles A. Dana Research Institute, Department of Medicine, Beth Israel Hospital, Boston, Massachusetts 02215.
authors.forename: L X
authors.initials: LX
authors.lastname: Liu
authors.forename: P F
authors.initials: PF
authors.lastname: Weller
mesh_terms: D000818:Animals; D002009:Brugia / Q000472:pathogenicity*; D006152:Cyclic GMP / Q000097:blood; D005849:Gerbillinae; D006801:Humans; D008842:Microfilariae / Q000472:pathogenicity; D010974:Platelet Aggregation; D011453:Prostaglandins / Q000502:physiology*
chemical_list: D011453:Prostaglandins; D006152:Cyclic GMP