Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
Cytometry A. 2010 Jun;77(6):515-23. doi: 10.1002/cyto.a.20879.
Intraerythrocytic maturation of the malaria parasite Plasmodium falciparum is associated with profound changes in the asymmetry of phospholipids in the lipid bilayer of the parasitized red blood cells (pRBCs). These changes may contribute to adherence of pRBCs to endothelial cells. This study investigates the effect of febrile temperature and proinflammatory cytokines on phosphatidylserine (PS) expression on the exofacial surface of pRBCs during parasite maturation. The expression of PS on the pRBCs was determined by flow cytometry using fluorescein-labeled annexin V, which specifically binds to PS and a vital nucleic acid fluorochrome for parasite staining. The results showed that PS expression on the surface of pRBCs increased in association with parasite maturation, especially at the late parasite stage. Furthermore, the growth of P. falciparum also accelerated senescence of the uninfected RBCs in parasite cultures. Exposure to febrile temperature led to significant increases in the expression of PS on the surface of pRBCs, particularly at the late parasite stage associated with the virulence strain of the parasite. In contrast, proinflammatory cytokines had no detectable effect on PS expression on pRBCs. These data suggest that PS molecule expression is more dependent on fever, parasitemia, parasite strain, and virulence than on cytokine exposure. These findings contribute to our understanding of the factors that are involved in malaria pathogenesis.
疟原虫裂殖子在红细胞内的成熟过程伴随着疟原虫感染红细胞(pRBC)双层脂膜中磷脂不对称性的深刻变化。这些变化可能有助于 pRBC 与内皮细胞的黏附。本研究探讨了发热温度和促炎细胞因子对寄生虫成熟过程中 pRBC 表面磷脂酰丝氨酸(PS)表达的影响。使用荧光素标记的 annexin V 通过流式细胞术测定 PS 在 pRBC 表面的表达,该 annexin V 特异性结合 PS 并可对寄生虫进行荧光染色。结果表明,PS 在 pRBC 表面的表达随着寄生虫的成熟而增加,特别是在晚期寄生虫阶段。此外,恶性疟原虫的生长也加速了寄生虫培养中未感染 RBC 的衰老。发热温度的暴露导致 pRBC 表面 PS 表达显著增加,尤其是与寄生虫毒力株相关的晚期寄生虫阶段。相比之下,促炎细胞因子对 pRBC 表面 PS 表达没有明显影响。这些数据表明 PS 分子的表达更多地依赖于发热、寄生虫血症、寄生虫株和毒力,而不是细胞因子暴露。这些发现有助于我们理解参与疟疾发病机制的因素。