Libby P, Alroy J, Pereira M E
J Clin Invest. 1986 Jan;77(1):127-35. doi: 10.1172/JCI112266.
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 a 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 less than 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.
克氏锥虫可引发恰加斯心脏病，这是拉丁美洲一个主要的公共卫生问题。人们对这种原生动物寄生虫与宿主细胞相互作用的机制了解甚少。我们最近发现，克氏锥虫具有感染性的锥鞭毛体形式表现出神经氨酸酶活性，并且能够使哺乳动物红细胞去唾液酸化。然而，尚不清楚克氏锥虫是否也能修饰心血管细胞的表面，而这些细胞直接参与了该疾病最重要的临床表现。因此，本研究确定了克氏锥虫是否能从培养的大鼠心肌细胞或人血管内皮细胞中去除唾液酸。用前体3H-N-乙酰-D-甘露糖胺对唾液酸进行代谢标记。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，导致心肌细胞中标记物质的显著释放（例如，2174±27 dpm/h，而自发释放为306±30 dpm/h，n = 4，P小于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物质是唾液酸。完整的克氏锥虫锥鞭毛体也以浓度依赖的方式从代谢标记的心机细胞中释放唾液酸。相比之下，克氏锥虫的一种非感染性形式，即无鞭毛体，不会使这些细胞去唾液酸化。半乳糖氧化酶标记显示，在用克氏锥虫神经氨酸酶处理的心肌细胞表面出现了新的去唾液酸化糖蛋白。通过花生凝集素（一种在去除末端唾液酸残基后与复合寡糖部分结合的凝集素）结合位点的出现，从组织化学上证实了心肌细胞的去唾液酸化。通过组织化学和代谢标记研究均确定，克氏锥虫神经氨酸酶也能从成人隐静脉内皮细胞中去除唾液酸。因此，克氏锥虫的感染性形式可通过去唾液酸化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初始相互作用中发挥作用。
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