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钩盲蛇蛛毒液及其神经鞘磷脂酶组分触发人和兔血小板的主要功能。

Loxosceles gaucho spider venom and its sphingomyelinase fraction trigger the main functions of human and rabbit platelets.

机构信息

Laboratório de Fisiopatologia, Instituto Butantan, São Paulo-SP, Brazil.

出版信息

Hum Exp Toxicol. 2011 Oct;30(10):1567-74. doi: 10.1177/0960327110393761. Epub 2011 Jan 19.

Abstract

Loxosceles venoms can promote severe local and systemic damages. We have previously reported that Loxosceles gaucho spider venom causes a severe early thrombocytopenia in rabbits. Herein, we investigated the in vitro effects of this venom and its sphingomyelinase fraction on the main functions of platelets. Whole venom and its fraction induced aggregation of both human and rabbit platelets. Aggregation was dependent of plasma component(s) but independent of venom-induced lysophosphatidic acid generation. There was no increase in the levels of lactate dehydrogenase during platelet aggregation, ruling out the possibility of platelet lysis. The increased expression of ligand-induced binding site 1 (LIBS1) induced by L. gaucho venom and its sphingomyelinase fraction, as well as of P-selectin by the whole venom, evidenced the activation state of both human and rabbit platelets. Adhesion assays showed an irregular response when platelets were exposed to the whole venom, whereas the sphingomyelinase fraction induced a dose-dependent increase in the platelet adhesion to collagen. These findings evidence that L. gaucho venom and its sphingomyelinase fraction trigger adhesion, activation, and aggregation of both human and rabbit platelets. Thus, this work justifies the use of rabbits to investigate Loxosceles venom-induced platelet disturbances, and it also supports research on the role of platelets in the pathogenesis of loxoscelism.

摘要

漏斗网蜘蛛毒液可导致严重的局部和全身损伤。我们之前曾报道过,沟纹漏斗蛛毒液可导致兔发生严重的早期血小板减少症。在此,我们研究了该毒液及其神经鞘磷脂酶组分对血小板主要功能的体外影响。全毒液及其组分可诱导人和兔血小板聚集。聚集依赖于血浆成分,但与毒液诱导的溶血磷脂酸生成无关。在血小板聚集过程中,乳酸脱氢酶水平没有升高,排除了血小板裂解的可能性。沟纹漏斗蛛毒液及其神经鞘磷脂酶组分诱导配体诱导结合位点 1(LIBS1)表达增加,以及全毒液诱导 P-选择素表达增加,表明人和兔血小板均处于激活状态。黏附试验表明,当血小板暴露于全毒液时会出现不规则反应,而神经鞘磷脂酶组分可诱导血小板对胶原蛋白的黏附呈剂量依赖性增加。这些发现表明,沟纹漏斗蛛毒液及其神经鞘磷脂酶组分可触发人和兔血小板的黏附、激活和聚集。因此,本研究证实了使用兔来研究漏斗网蜘蛛毒液诱导的血小板紊乱的合理性,同时也支持了血小板在类蝎螫伤发病机制中的作用的研究。

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