Church James A, Nyamako Lydia, Olupot-Olupot Peter, Maitland Kathryn, Urban Britta C
Centre for Paediatrics, Blizard Institute, Queen Mary University of London, London, UK.
KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya.
Malar J. 2016 Feb 1;15:54. doi: 10.1186/s12936-016-1110-3.
Children with severe malaria are at increased risk of invasive bacterial disease particularly infection with enteric gram-negative organisms. These organisms are likely to originate from the gut, however, how and why they breach the intestinal interface in the context of malaria infection remains unclear. One explanation is that accumulation of infected red blood cells (iRBCs) in the intestinal microvasculature contributes to tissue damage and subsequent microbial translocation which can be addressed through investigation of the impact of cytoadhesion in patients with malaria and intestinal damage.
Using a static adhesion assay, cytoadhesion of iRBCs was quantified in 48 children with malaria to recombinant proteins constitutively expressed on endothelial cell surfaces. Cytoadhesive phenotypes between children with and without biochemical evidence of intestinal damage [defined as endotoxemia or elevated plasma intestinal fatty acid binding protein (I-FABP)] was compared.
The majority of parasites demonstrated binding to the endothelial receptors CD36 and to a lesser extent to ICAM-1. Reduced adhesion to CD36 but not adhesion to ICAM-1 or rosetting was associated with malarial anaemia (p = 0.004). Increased adhesion of iRBCs to ICAM-1 in children who had evidence of elevated I-FABP (p = 0.022), a marker of intestinal ischaemia was observed. There was no correlation between the presence of endotoxemia and increased adhesion to any of the recombinant proteins.
Increased parasite adhesion to ICAM-1 in children with evidence of intestinal ischaemia lends further evidence to a link between the cytoadherence of iRBCs in gut microvasculature and intestinal damage.
重症疟疾患儿发生侵袭性细菌感染的风险增加，尤其是肠道革兰氏阴性菌感染。这些细菌可能源自肠道，然而，在疟疾感染的情况下它们如何以及为何突破肠道界面仍不清楚。一种解释是，肠道微血管中感染的红细胞（iRBCs）积聚导致组织损伤及随后的微生物易位，这可通过研究细胞黏附对疟疾患者肠道损伤的影响来解决。
采用静态黏附试验，对48例疟疾患儿的iRBCs与内皮细胞表面组成性表达的重组蛋白的细胞黏附进行定量。比较有和没有肠道损伤生化证据[定义为内毒素血症或血浆肠道脂肪酸结合蛋白（I-FABP）升高]的患儿之间的细胞黏附表型。
大多数寄生虫表现出与内皮受体CD36结合，与细胞间黏附分子-1（ICAM-1）的结合程度较低。与CD36的黏附减少而非与ICAM-1的黏附或红细胞凝聚与疟疾贫血相关（p = 0.004）。在有I-FABP升高证据（p = 0.022）的患儿中观察到iRBCs与ICAM-1的黏附增加，I-FABP是肠道缺血的标志物。内毒素血症的存在与对任何重组蛋白的黏附增加之间无相关性。
有肠道缺血证据的患儿中寄生虫与ICAM-1的黏附增加，进一步证明了肠道微血管中iRBCs的细胞黏附与肠道损伤之间的联系。
