Intravascular filarial parasites inhibit platelet aggregation. Role of parasite-derived prostanoids.
Intravascular filarial parasites inhibit platelet aggregation. Role of parasite-derived prostanoids.
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DOI：
10.1172/jci115691
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发表时间：
1992-04
期刊：
影响因子：
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通讯作者：
L. Liu;P. Weller
中科院分区：
文献类型：
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作者：
L. Liu;P. Weller
导致人类淋巴丝虫病的线虫寄生虫尽管持续暴露在宿主细胞中，但仍在其血管栖息地长期存活。血小板不附着于血液传播的微丝虫，在循环微丝虫患者中没有观察到血栓闭塞现象。我们研究了微丝虫在体外抑制人血小板聚集的能力。马来丝虫微丝虫与人血小板孵育后，可剂量依赖地抑制激动剂诱导的血小板聚集、血栓烷生成和5-羟色胺释放。每10(4)个血小板中只有一个微丝虫可完全抑制凝血酶、胶原、花生四烯酸或离子载体A23187诱导的血小板聚集。微丝虫还能抑制由ADP、化合物U46619或血小板激活因子刺激的富含血小板的血浆中的血小板聚集。这种抑制需要寄生虫和血小板之间的密切接触，而不是直接接触，并且是由寄生虫来源的低分子量(小于1,000 mR)的可溶性因子介导的，这些因子在水介质中不稳定，导致血小板cAMP升高。用药物环氧合酶抑制剂预先治疗微丝虫可以减少寄生虫对前列环素和前列腺素E_2的释放，并减少微丝虫对血小板聚集的抑制。这些结果表明，微丝虫抑制血小板聚集的机制可能包括精制抗聚集二十烷类化合物。
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.