A NEURAMINIDASE FROM TRYPANOSOMA-CRUZI REMOVES SIALIC-ACID FROM THE SURFACE OF MAMMALIAN MYOCARDIAL AND ENDOTHELIAL-CELLS
A NEURAMINIDASE FROM TRYPANOSOMA-CRUZI REMOVES SIALIC-ACID FROM THE SURFACE OF MAMMALIAN MYOCARDIAL AND ENDOTHELIAL-CELLS
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DOI：
10.1172/jci112266
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发表时间：
1986-01-01
影响因子：
15.9
通讯作者：
PEREIRA, MEA
中科院分区：
文献类型：
--
作者：
LIBBY, P;ALROY, J;PEREIRA, MEA
克氏锥虫引起恰加斯心脏病，这是拉丁美洲的一个主要公共卫生问题。这种原生动物寄生虫与宿主细胞相互作用的机制尚不清楚。我们最近发现，感染性锥鞭毛体形式的克氏锥虫表现出神经氨酸酶活性，并且可以使哺乳动物红细胞脱唾液酸化。然而，目前尚不清楚克氏锥虫是否也可以改变直接参与该疾病最重要临床表现的心血管细胞的表面。因此，本研究确定了克氏锥虫是否可以去除培养的大鼠心肌或人血管内皮细胞中的唾液酸。唾液酸用前体 3H-N-乙酰基-D-甘露糖胺进行代谢标记。从完整的克氏锥虫锥鞭毛体中分离出的可溶性神经氨酸酶导致心肌细胞显着释放标记物质（例如，2,174 .+-. 27 dpm/h 与自发释放 306 .+-. 30 dpm/h，n = 4，P < 0.001）。 色谱分析表明克氏锥虫神经氨酸酶释放的大部分放射性是唾液酸。完整的克氏锥虫锥鞭毛体还以浓度依赖性方式从代谢标记的心肌细胞中释放唾液酸。相比之下，克氏锥虫的非感染性无鞭毛体不会使这些细胞去唾液酸化。半乳糖氧化酶标记证明用克氏锥虫神经氨酸酶处理的心肌细胞表面有新的去唾液酸化糖蛋白。心肌细胞的去唾液酸化通过花生凝集素结合位点的出现在组织化学上得到证实，花生凝集素是一种凝集素，在去除末端唾液酸残基后与复杂的寡糖部分结合。根据组织化学和代谢标记研究的结果，克氏锥虫神经氨酸酶还可以去除成人隐静脉内皮细胞中的唾液酸。因此，感染性克氏锥虫可以通过脱唾液酸作用对心肌和血管内皮细胞的表面进行化学修饰。这种改变可能在这种寄生虫与宿主心血管系统的这些重要靶细胞的最初相互作用中发挥作用。
Trypanosoma cruzi causes Chagasic heart disease, a major public health problem in Latin America. The mechanism of interaction of this protozooan parasite with host cells is poorly understood. We recently found that the infective trypomastigote form of T. cruzi exhibits neuraminidase activity and can desialylate mammalian erythrocytes. However, it is not known if T. cruzi can also modify the surfaces of cardiovascular cells that are directly involved in the most important clinical manifestations of this disease. Accordingly, this study determined whether T. cruzi can remove sialic acid from cultured rat myocardial or human vascular endothelial cells. Sialic acid was labeled metabolically with the precursor 3H-N-acetyl-D-mannosamine. Soluble neuraminidase, isolated from intact T. cruzi trypomastigotes, caused significant release of labeled material from myocardial cells (e.g., 2,174 .+-. 27 dpm/h vs. spontaneous release of 306 .+-. 30 dpm/h, n = 4, P < 0.001). Chromatographic analysis showed that the bulk of the radioactivity released by T. cruzi neuraminidase was sialic acid. Intact T. cruzi trypomastigotes also released sialic acid from metabolically labeled myocardial cells in a concentration-dependent manner. In contrast, a noninfective form of T. cruzi, the amastigote, did not desialylate these cells. Galactose oxidase labeling demonstrated newly desialylated glycoproteins on the surface of myocardial cells treated with T. cruzi neuraminidase. Desialylation of myocardial cells was confirmed histochemically by the appearance of binding sites for peanut agglutinin, a lectin that binds to complex oligosaccharide moieties after removal of the terminal sialyl residue. T. cruzi neuraminidase also removed sialic acid from adult human saphenous vein endothelial cells, as determined by both histochemical and metabolic labeling studies. Thus, infective forms of T. cruzi can chemically modify the surfaces of myocardial and vascular endothelial cells by desialylation. This alteration may play a role in the initial interaction of this parasite with these important target cells of the host cardiovascular system.