ERYTHROCYTIC MECHANISM OF SICKLE-CELL RESISTANCE TO MALARIA

ERYTHROCYTIC MECHANISM OF SICKLE-CELL RESISTANCE TO MALARIA
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DOI:
10.1073/pnas.75.4.1994
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发表时间:
1978-01-01
影响因子:
11.1
通讯作者:
FRIEDMAN, MJ
FRIEDMAN, MJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
FRIEDMAN, MJ

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具有镰状细胞性状的个体对恶性疟的抵抗力的生理基础尚未被理解。红细胞恶性疟原虫培养的最新进展使得直接研究镰状细胞血红蛋白细胞中疟原虫的发展成为可能。在高氧(18%)环境中,细胞无明显镰状化,恶性疟原虫在正常(AA)、Hb S纯合子(SS)和Hb S杂合子(SA)红细胞中的生长和增殖是相同的。低O2(1-5%)下的培养物显示出明显的生长抑制。SS红细胞的镰状化杀死并溶解大部分或全部细胞内寄生虫。SA红细胞中的寄生虫主要在大环期被杀死,可能是寄生虫代谢中断的结果。培养前,在氰酸盐中孵育,逆转了SA红细胞对疟原虫生长的抗性,但对SS红细胞镰状化或抗性没有影响。体内耐药机制可能仅是由于红细胞内条件。
The physiological basis for the resistance to falciparum malaria of individuals with sickle cell trait has not been understood. Recent advances in erythrocytic Plasmodium falciparum culture made possible a direct investigation of the development of the malaria parasite in cells with sickle cell hemoglobin. In a high (18%) O2 atmosphere, ther is no apparent sickling of cells and the growth and multiplication of P. falciparum is identical in normal (AA), Hb S homozygous (SS), and Hb S heterozygous (SA) erythrocytes. Cultures under low (1-5%) O2 showed clear inhibition of growth. The sickling of SS red cells killed and lysed most or all of the intracellular parasites. Parasites in SA red cells were killed primarily at the large ring stage, probably as a result of a disruption of the parasite metabolism. Incubation in cyanate, prior to culture, reversed the resistance of SA erythrocytes to plasmodial growth, but had no effect on SS red cell sickling or resistance. The mechanism of resistance in vivo may be due solely to intraerythrocytic conditions.