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纯化的人嗜酸性粒细胞颗粒蛋白对旋毛虫新生幼虫的比较毒性

Comparative toxicity of purified human eosinophil granule proteins for newborn larvae of Trichinella spiralis.

作者信息

Hamann K J, Barker R L, Loegering D A, Gleich G J

出版信息

J Parasitol. 1987 Jun;73(3):523-9.

PMID:3598802
Abstract

Eosinophils have been implicated in both in vivo and in vitro destruction of helminths. One approach toward elucidating the role of the eosinophil in parasite killing has been to test the toxicity of purified eosinophil granule proteins for parasites in vitro. Previously, major basic protein (MBP) and eosinophil cationic protein (ECP) were shown to be toxic for schistosomules of Schistosoma mansoni, while eosinophil-derived neurotoxin (EDN) was only marginally so. We tested the toxicity of MBP, ECP, and EDN over a range of concentrations (0.006-5 X 10(-4) M) for newborn larvae of Trichinella spiralis. Our observations confirm previous reports of toxicity of mildly reduced and alkylated (R & A) MBP. At concentrations of 5 X 10(-5) M and above, R & A MBP killed 75% or more of the larvae within the first hour of culture. ECP was an effective toxin for these larvae after 3 hr of culture, and by 12 hr, dose-related toxicity was evident. After 24 hr, 100% of the larvae were killed at 5 X 10(-5) M ECP. EDN was much less toxic; after 12 hr, 90% of the larvae survived at concentrations of 1 X 10(4) M, while 5 X 10(-4) M EDN killed all the larvae. At the optimal toxic concentrations of 5 X 10(-5) M ECP and 5 X 10(-4) M EDN, kinetics of killing by these 2 proteins were essentially the same. Thus, on a molecular basis, both MBP and ECP appear to be potent helminthotoxins whereas EDN is much less so.

摘要

嗜酸性粒细胞在体内和体外对蠕虫的破坏中都发挥了作用。阐明嗜酸性粒细胞在杀死寄生虫过程中作用的一种方法是在体外测试纯化的嗜酸性粒细胞颗粒蛋白对寄生虫的毒性。此前,已证明主要碱性蛋白(MBP)和嗜酸性粒细胞阳离子蛋白(ECP)对曼氏血吸虫的童虫具有毒性,而嗜酸性粒细胞衍生神经毒素(EDN)的毒性则很微弱。我们测试了MBP、ECP和EDN在一系列浓度(0.006 - 5×10⁻⁴ M)下对旋毛虫新生幼虫的毒性。我们的观察结果证实了先前关于轻度还原和烷基化(R&A)MBP毒性的报道。在浓度为5×10⁻⁵ M及以上时,R&A MBP在培养的第一小时内杀死了75%或更多的幼虫。培养3小时后,ECP对这些幼虫是一种有效的毒素,到12小时时,剂量相关的毒性明显。24小时后,5×10⁻⁵ M ECP杀死了所有幼虫。EDN的毒性要小得多;12小时后,在1×10⁻⁴ M的浓度下,90%的幼虫存活,而5×10⁻⁴ M EDN杀死了所有幼虫。在5×10⁻⁵ M ECP和5×10⁻⁴ M EDN的最佳毒性浓度下,这两种蛋白质的杀伤动力学基本相同。因此,从分子层面来看,MBP和ECP似乎都是强效的杀蠕虫毒素,而EDN的毒性则小得多。

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Comparative toxicity of purified human eosinophil granule proteins for newborn larvae of Trichinella spiralis.纯化的人嗜酸性粒细胞颗粒蛋白对旋毛虫新生幼虫的比较毒性
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