Fresh isolates from children with severe Plasmodium falciparum malaria bind to multiple receptors

Fresh isolates from children with severe Plasmodium falciparum malaria bind to multiple receptors
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DOI:
10.1128/iai.69.9.5849-5856.2001
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发表时间:
2001-09-01
影响因子:
3.1
通讯作者:
Marsh, K
Marsh, K
中科院分区:
医学2区
文献类型:
--
作者:
Heddini, A;Pettersson, F;Marsh, K

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隔离恶性疟原虫感染的红细胞(pRBC)远离外周循环是所有现场分离株的特性。在这里,我们已经检查了111个新鲜的临床分离的pRBC与疟疾儿童的一些粘附功能,以研究他们可能的共表达和疾病的严重程度。进行了大量的粘附试验,研究玫瑰花结、巨玫瑰花结以及与CD 36、细胞间粘附分子1、血小板内皮细胞粘附分子1、血小板反应蛋白、肝素、血型A和免疫球蛋白的结合。悬浮试验在分离株的实际寄生虫血症下进行,而所有静态粘附试验在相等的调整寄生虫血症下进行。与多种受体结合的能力,以及形成罗氏和巨罗氏的能力,被认为是更频繁的分离,从儿童与轻度疟疾严重(P = 0.0015)。与轻度疟疾儿童相比,重度疟疾儿童更常出现罗氏沼虾和巨罗氏沼虾,细胞聚集体更大、更紧密(P = 0.0023)。免疫球蛋白(97%的分离株)和肝素(81%的分离株)与感染红细胞的结合是常见的,与肝素和血型A的结合与疾病的严重程度相关(分别为P = 0.011和P = 0.031)。这些结果支持了这样的想法,即与多种受体结合的分离株参与了严重疟疾的病因,并且几种受体-配体相互作用协同作用导致严重疾病。
The sequestration of Plasmodium falciparum-infected erythrocytes (pRBC) away from the peripheral circulation is a property of all field isolates. Here we have examined the pRBC of 111 fresh clinical isolates from children with malaria for a number of adhesive features in order to study their possible coexpression and association with severity of disease. A large number of adhesion assays were performed studying rosetting, giant rosetting, and binding to CD36, intercellular adhesion molecule 1, platelet endothelial cell adhesion molecule 1, thrombospondin, heparin, blood group A, and immunoglobulins. Suspension assays were performed at the actual parasitemia of the isolate, while all the static adhesion assays were carried out at an equal adjusted parasitemia. The ability to bind to multiple receptors, as well as the ability to form rosettes and giant rosettes, was found to be more frequent among isolates from children with severe versus mild malaria (P = 0.0015). Rosettes and giant rosettes were more frequent for children with severe malaria, and the cell aggregates were larger and tighter, than for those with mild disease (P = 0.0023). Binding of immunoglobulins (97% of isolates) and of heparin (81% of isolates) to infected erythrocytes was common, and binding to heparin and blood group A was associated with severity of disease (P = 0.011 and P = 0.031, respectively). These results support the idea that isolates that bind to multiple receptors are involved in the causation of severe malaria and that several receptor-ligand interactions work synergistically in bringing about severe disease.