Febrile temperatures induce cytoadherence of ring-stage Plasmodium falciparum-infected erythrocytes
Febrile temperatures induce cytoadherence of ring-stage Plasmodium falciparum-infected erythrocytes
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DOI：
10.1073/pnas.172398999
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发表时间：
2002-09-03
影响因子：
11.1
通讯作者：
White, NJ
中科院分区：
文献类型：
--
作者：
Udomsangpetch, R;Pipitaporn, B;White, NJ
在恶性疟疾中，疟疾寄生虫诱导受感染的红细胞表面发生变化，导致粘附在血管内皮和其他红细胞上。因此，较成熟阶段的恶性疟原虫被隔离在微血管中，导致重要器官功能障碍，而环期则在血流中循环。疟疾的特点是发烧。我们在体外研究了发热温度对恶性疟原虫感染红细胞细胞粘附性的影响。从10例急性恶性疟疾患者新获得的环期感染红细胞不粘附主要血管粘附受体CD36或细胞间粘附分子-1 （ICAM-1）。然而，在短暂加热到40度后，所有环感染的红细胞都粘附在CD36上，一些分离物粘附在ICAM-1上，而在37度孵育的对照组则没有。加热至40℃可加速细胞粘附，最大细胞粘附量增加一倍（P < 0.01）。被ICAM-1结合克隆A4var的环状阶段感染的红细胞在37℃时也没有细胞粘附，但在加热到与CD36和ICAM-11结合的发热温度后才发生细胞粘附。通过短暂加热，感染滋养体的红细胞的粘附性也大大增加。热诱导粘附的因素被证明是寄生虫衍生的变异表面蛋白PfEMP-11。RNA分析显示，在加热和未加热的环期寄生虫中，var mRNA的水平没有差异。因此，发热诱导的粘附似乎与PfEMP-11向红细胞膜的运输增加有关。发热引起的细胞粘附可能具有重要的病理后果，并可能解释重症疟疾患者发热后的临床恶化和退热药物对寄生虫清除的影响。
In falciparum malaria, the malaria parasite induces changes at the infected red blood cell surface that lead to adherence to vascular endothelium and other red blood cells. As a result, the more mature stages of Plasmodium falciparum are sequestered in the microvasculature and cause vital organ dysfunction, whereas the ring stages circulate in the blood stream. Malaria is characterized by fever. We have studied the effect of febrile temperatures on the cytoadherence in vitro of A falciparum-infected erythrocytes. Freshly obtained ring-stage-infected red blood cells from 10 patients with acute falciparum malaria did not adhere to the principle vascular adherence receptors CD36 or intercellular adhesion molecule-1 (ICAM-1). However, after a brief period of heating to 40degreesC, all ring-infected red blood cells adhered to CD36, and some isolates adhered to ICAM-1, whereas controls incubated at 37degreesC did not. Heating to 40degreesC accelerated cytoadherence and doubled the maximum cytoadherence observed (P < 0.01). Erythrocytes infected by ring-stages of the ICAM-1 binding clone A4var also did not cytoadhere at 37degreesC, but after heating to febrile temperatures bound to both CD36 and ICAM-11. Adherence of red blood cells infected with trophozoites was also increased considerably by brief heating. The factor responsible for heat induced adherence was shown to be the parasite derived variant surface protein PfEMP-11. RNA analysis showed that levels of var mRNA did not differ between heated and unheated ring-stage parasites. Thus fever-induced adherence appeared to involve increased trafficking of PfEMP-11 to the erythrocyte membrane. Fever induced cytoadherence is likely to have important pathological consequences and may explain both clinical deterioration with fever in severe malaria and the effects of antipyretics on parasite clearance.