ANALYSES OF MECHANISMS FOR PLASMODIUM ADAPTATION TO THE HOST ERYTHROCYTES

为了获得开发疟疾疫苗和新型抗疟药所需的基本知识，人们在分子和细胞水平上研究了疟疾寄生虫对其宿主红细胞的适应机制。结果如下：1。疟疾感染细胞中代谢物的膜转运。(1)恶性疟原虫在人红细胞中生长良好，用乌阿因治疗大大降低了红细胞的钾水平。(2) P. yoeli感染细胞的膜上出现小孔隙，导致2-脱氧-d -葡萄糖的摄取增加。质子的电势穿过红细胞内寄生虫的质膜与向上的2-脱氧-d -葡萄糖的主动摄取相耦合。(3)黄杨线粒体具有内负膜电位。恶性疟原虫卵生子表面抗原的多态性。(1)克隆并测序了恶性疟原虫主要子体表面抗原前体基因（p190）。对几种寄生虫分离物的p190基因进行比较，发现了保守区和可变区。(2)序列变异不具有广泛的多态性，但可分为两种类型。对14株分离株基因组DNA的Southern blot分析表明p190基因为二态等位基因。这表明p190等位基因的基因内重组产生了抗原的多态性。疟疾感染红细胞的钙代谢。(1) Ca^<2+>离子载体、钙拮抗剂和钙调素抑制剂干扰约氏疟原虫和恶性疟原虫感染细胞的钙代谢，导致寄生虫死亡。

To obtain fundamental knowledge necessary for developing malaria vaccines and new antimalarials, mechanisms for adaptation by malaria parasites to their host erythrocytes have been studied at the molecular and cellular levels. Results are as follows:I. Membrane transport of metabolites in malaria-infected cells. (1) Plasmodium falciparum grows well in human erythrocytes, whose potassium levels ae reduced greatly by treatment with ouabain. (2) An appearance of small pores in the membranes of P. yoelii-infected cells lead to increase in the uptake of 2-deoxy-D-glucose. An electrical potential of protons across the plasma membrane of intraerythrocytic parasites is coupled to an uphill active uptake of 2-deoxy-D-glucose. (3) The mitochondrion of P. yoelii has an inside negative membrane potential.II. Polymorphism of a surface antigen of P. falciparum merozoite. (1) The gene for a precursor (p190) to major merozoite surface antigens of P. falciparum has been cloned and sequenced. Comparisons of the p190 gene from several parasite isolates has revealed both conserved and variable regions. (2) Variations in the sequence are not widely polymorphic but fall into two types. Southern blot analyses of genomic DNA from 14 isolates has shown that the p190 gene is dimorphic alles. it is suggested that intragenic recombination of the p190 alles creates the antigen's polymorphism.III. Calcium metabolism of malaria-infected erythrocytes. (1) Disturbance of calcium metabolism of P. yoelii- and P. falciparum-infected cells by Ca^<2+> ionophore, calcium antagonists and calmodulin inhibitors results in the death of the parasites.