Lang Philipp A, Kasinathan Ravi S, Brand Verena B, Duranton Christophe, Lang Camelia, Koka Saisudha, Shumilina Ekaterina, Kempe Daniela S, Tanneur Valerie, Akel Ahmad, Lang Karl S, Foller Michael, Kun Jurgen F J, Kremsner Peter G, Wesselborg Sebastian, Laufer Stefan, Clemen Christoph S, Herr Claudia, Noegel Angelika A, Wieder Thomas, Gulbins Erich, Lang Florian, Huber Stephan M
Department of Physiology, University of Tübingen, Germany.
Cell Physiol Biochem. 2009;24(5-6):415-28. doi: 10.1159/000257529. Epub 2009 Nov 4.
The course of malaria does not only depend on the virulence of the parasite Plasmodium but also on properties of host erythrocytes. Here, we show that infection of erythrocytes from human sickle cell trait (HbA/S) carriers with ring stages of P. falciparum led to significantly enhanced PGE(2) formation, Ca(2+) permeability, annexin-A7 degradation, phosphatidylserine (PS) exposure at the cell surface, and clearance by macrophages. P. berghei-infected erythrocytes from annexin-A7-deficient (annexin-A7(-/-)) mice were more rapidly cleared than infected wildtype cells. Accordingly, P. berghei-infected annexin-A7(-/-) mice developed less parasitemia than wildtype mice. The cyclooxygenase inhibitor aspirin decreased erythrocyte PS exposure in infected annexin-A7(-/-) mice and abolished the differences of parasitemia and survival between the genotypes. Conversely, the PGE(2)-agonist sulprostone decreased parasitemia and increased survival of wild type mice. In conclusion, PS exposure on erythrocytes results in accelerated clearance of Plasmodium ring stage-infected HbA/S or annexin-A7(-/-) erythrocytes and thus confers partial protection against malaria in vivo.
疟疾的病程不仅取决于疟原虫的毒力，还取决于宿主红细胞的特性。在此，我们表明，用恶性疟原虫环状体感染人类镰状细胞性状（HbA/S）携带者的红细胞，会导致前列腺素E2（PGE2）生成显著增强、钙离子通透性增加、膜联蛋白A7降解、细胞表面磷脂酰丝氨酸（PS）暴露以及被巨噬细胞清除。来自膜联蛋白A7缺陷（膜联蛋白A7-/-）小鼠的感染伯氏疟原虫的红细胞比感染的野生型细胞清除得更快。相应地，感染伯氏疟原虫的膜联蛋白A7-/-小鼠的寄生虫血症比野生型小鼠轻。环氧化酶抑制剂阿司匹林可降低感染的膜联蛋白A7-/-小鼠红细胞的PS暴露，并消除基因型之间寄生虫血症和生存率的差异。相反，PGE2激动剂舒前列素可降低野生型小鼠的寄生虫血症并提高其生存率。总之，红细胞上的PS暴露会导致疟原虫环状体感染的HbA/S或膜联蛋白A7-/-红细胞的清除加速，从而在体内赋予对疟疾的部分保护作用。
