Eda Shigetoshi, Sherman Irwin W
Department of Biology, University of California Riverside, 92521, USA.
Cell Physiol Biochem. 2002;12(5-6):373-84. doi: 10.1159/000067908.
Phosphatidylserine (PS) is a membrane phospholipid which in intact cells is exclusively localized in the inner leaflet of the lipid bilayer. However, once cells undergo apoptosis or oxidative stress, PS molecules are exposed on the external surface of the cells and this contributes to their adherence to macrophages or endothelial cells. PS exposure on Plasmodium falciparum-infected red cells was determined by flow cytometry using fluorescein-labeled annexin V, which specifically binds to PS. Involvement of exposed PS in the adherence of malaria-infected red cells to endothelial cells was examined by in vitro cytoadherence assays. Infected cells exposed PS on their surface as the intracellular parasites matured to trophozoite and schizont stages. Adherence of malaria-infected cells to CD36, CD36-expressing Chinese hamster ovary cells, thrombospondin, and C32 amelanotic melanoma cells was inhibited by annexin V, whereas ICAM-1- and chondroitin sulfate A-mediated binding was not. Further, PS liposomes and glycerophosphorylserine, but not phosphatidylcholine liposomes and glycerophosphorylcholine, inhibited the binding of infected cells to CD36 and thrombospondin. In conclusion, these results demonstrate that PS exposed on the surface of malaria-infected red cells contributes, in part, to the adherence of P. falciparum-parasitized red cells to CD36 and thrombospondin.
磷脂酰丝氨酸(PS)是一种膜磷脂,在完整细胞中仅定位于脂质双层的内小叶。然而,一旦细胞经历凋亡或氧化应激,PS分子就会暴露在细胞外表面,这有助于它们与巨噬细胞或内皮细胞黏附。使用荧光素标记的膜联蛋白V通过流式细胞术测定恶性疟原虫感染红细胞上的PS暴露情况,膜联蛋白V可特异性结合PS。通过体外细胞黏附试验检测暴露的PS在疟疾感染红细胞与内皮细胞黏附中的作用。随着细胞内寄生虫成熟为滋养体和裂殖体阶段,感染细胞在其表面暴露PS。膜联蛋白V可抑制疟疾感染细胞与CD36、表达CD36的中国仓鼠卵巢细胞、血小板反应蛋白和C32无黑色素黑色素瘤细胞的黏附,而ICAM-1和硫酸软骨素A介导的结合则不受影响。此外,PS脂质体和甘油磷酰丝氨酸可抑制感染细胞与CD36和血小板反应蛋白的结合,而磷脂酰胆碱脂质体和甘油磷酰胆碱则无此作用。总之,这些结果表明,疟疾感染红细胞表面暴露的PS部分促成了恶性疟原虫寄生红细胞与CD36和血小板反应蛋白的黏附。