Alsam Selwa, Kim Kwang Sik, Stins Monique, Rivas Antonio Ortega, Sissons James, Khan Naveed Ahmed
School of Biological and Chemical Sciences, Birkbeck College, University of London, WC1E 7HX, England, London, UK.
Microb Pathog. 2003 Dec;35(6):235-41. doi: 10.1016/j.micpath.2003.07.001.
Acanthamoeba are opportunistic protozoan parasites that can cause fatal granulomatous amoebic encephalitis, however, the pathogenic mechanisms associated with this disease remain unclear. One of the primary factors in Acanthamoeba encephalitis is the haematogenous spread, followed by invasion of the blood-brain barrier resulting in the transmigration of Acanthamoeba into the central nervous system. In this study, we have used human brain microvascular endothelial cells, which constitute the blood-brain barrier and studied their interactions with Acanthamoeba. Using in vitro cultures, we showed that Acanthamoeba isolates belonging to genotypes T3, T4 and T11, exhibited increased cytotoxicity on human brain microvascular endothelial cells as well as exhibited higher binding and were considered potential pathogens. In contrast, Acanthamoeba isolates belonging to genotypes T2 and T7 exhibited minimal cytotoxicity and significantly less binding to human brain microvascular endothelial cells (P< 0.01). Furthermore, exogenous alpha-mannose inhibited binding but increased cytotoxicity of human brain microvascular endothelial cells. This is the first demonstration of Acanthamoeba interactions with primary human brain microvascular endothelial cells.
棘阿米巴是机会性原生动物寄生虫，可导致致命的肉芽肿性阿米巴脑炎，然而，与该疾病相关的致病机制仍不清楚。棘阿米巴脑炎的主要因素之一是血行播散，随后侵袭血脑屏障，导致棘阿米巴迁移至中枢神经系统。在本研究中，我们使用了构成血脑屏障的人脑微血管内皮细胞，并研究了它们与棘阿米巴的相互作用。通过体外培养，我们发现属于T3、T4和T11基因型的棘阿米巴分离株对人脑微血管内皮细胞表现出增强的细胞毒性，同时表现出更高的结合能力，被认为是潜在病原体。相比之下，属于T2和T7基因型的棘阿米巴分离株表现出最小的细胞毒性，与人脑微血管内皮细胞的结合明显较少（P<0.01）。此外，外源性α-甘露糖抑制了人脑微血管内皮细胞的结合，但增加了其细胞毒性。这是首次证明棘阿米巴与原代人脑微血管内皮细胞的相互作用。
