Roestenberg Meta, McCall Matthew, Mollnes Tom Eirik, van Deuren Marcel, Sprong Tom, Klasen Ina, Hermsen Cornelus C, Sauerwein Robert W, van der Ven André
Radboud University Nijmegen Medical Center, Postbus 9101, 6500 HB Nijmegen, The Netherlands.
Trans R Soc Trop Med Hyg. 2007 Jul;101(7):643-9. doi: 10.1016/j.trstmh.2007.02.023. Epub 2007 May 3.
The objective of this study was to investigate complement activation in uncomplicated, early phases of human malaria. Fifteen healthy volunteers were experimentally infected with Plasmodium falciparum malaria. Parasitemia and complement activation products were assessed. During blood stage parasitemia, volunteers showed a significant increase in soluble terminal complement complex (TCC) formation. After start of a curative regimen of artemether/lumefantrine, TCC further increased due to activation of both the classical and the alternative pathway. In-vitro studies confirmed activation of complement by parasite cultures. We thus detected an increase in complement activation in volunteers with experimentally induced malaria, even before parasitemia could be detected microscopically. This significant increase in complement activation occurred despite the possible control of TCC formation by complement regulatory proteins on erythrocytes and the extremely low levels of parasitemia. Treatment with artemether/lumefantrine was followed by classical and alternative pathway complement activation, without evidence for mannan-binding-lectin-mediated complement activation.
本研究的目的是调查人类疟疾非复杂性早期阶段的补体激活情况。15名健康志愿者通过实验感染了恶性疟原虫疟疾。对疟原虫血症和补体激活产物进行了评估。在血液阶段疟原虫血症期间，志愿者可溶性末端补体复合物（TCC）形成显著增加。在开始使用蒿甲醚/本芴醇治疗方案后，由于经典途径和替代途径的激活，TCC进一步增加。体外研究证实寄生虫培养可激活补体。因此，我们发现在实验性诱导疟疾的志愿者中，即使在显微镜下检测到疟原虫血症之前，补体激活就已增加。尽管红细胞上的补体调节蛋白可能控制TCC形成且疟原虫血症水平极低，但补体激活仍显著增加。使用蒿甲醚/本芴醇治疗后，经典途径和替代途径均激活补体，未发现甘露聚糖结合凝集素介导的补体激活证据。
