脑型疟疾患者脑毛细血管中与内皮糖萼相关的特定成分丢失。

C. Hempel, D. Milner, K. Seydel, T. Taylor
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引用次数: 3

摘要

背景:脑型疟疾(CM)是恶性疟原虫感染的一种罕见但严重且经常致命的结果。发病机制包括脑微血管中寄生红细胞的内皮活化和隔离。疟疾患者尿液和血浆中糖胺聚糖浓度升高,提示与内皮糖萼有关。方法采用凝集素组织化学方法,比较CM死亡和非疟疾性昏迷患儿脑毛细血管中多个糖表位的分布。结果与对照组相比,番茄凝集素检测到的n -乙酰氨基葡萄糖胺残留量在CM患儿中普遍降低。我们使用CM脑毛细血管中细胞间粘附分子-1和甘露糖残基的血管表达作为局部血管炎症的证据,CM患者中两者的表达均高于对照组。发现唾液酸残基在CM患者中显著减少。相比之下,在脑血管系统上经常检测到的其他糖表位的水平没有变化,这表明CM患者的大脑微血管有特异性重塑。结论本研究结果支持并扩展了早期关于严重疟疾患儿内皮糖萼破坏的报道。
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Specific components associated with the endothelial glycocalyx are lost from brain capillaries in cerebral malaria.
BACKGROUND Cerebral malaria (CM) is a rare, but severe and frequently fatal outcome of infections with Plasmodium falciparum. Pathogenetic mechanisms include endothelial activation and sequestration of parasitized erythrocytes in the cerebral microvessels. Increased concentrations of glycosaminoglycans in urine and plasma of malaria patients have been described, suggesting involvement of endothelial glycocalyx. METHODS We used lectin histochemistry on postmortem samples to compare the distribution of multiple sugar epitopes on cerebral capillaries in children who died from CM and from non-malarial comas. RESULTS N-acetyl glucosamine residues detected by tomato lectin are generally reduced in children with CM compared to controls. We used the vascular expression of intercellular adhesion molecule-1 and mannose residues on brain capillaries of CM as evidence of local vascular inflammation, and both were expressed more highly in CM patients than controls. Sialic acid residues were found to be significantly reduced in patients with CM. By contrast, the levels of other sugar epitopes regularly detected on the cerebral vasculature were unchanged, and this suggests specific remodeling of cerebral microvessels in CM patients. CONCLUSIONS Our findings support and expand upon earlier reports of disruptions of the endothelial glycocalyx in children with severe malaria.
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