PLASMODIUM-FALCIPARUM - PROTEASE INHIBITORS AND INHIBITION OF ERYTHROCYTE INVASION

PLASMODIUM-FALCIPARUM - PROTEASE INHIBITORS AND INHIBITION OF ERYTHROCYTE INVASION
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DOI:
10.1016/0014-4894(86)90050-0
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发表时间:
1986-12-01
影响因子:
2.1
通讯作者:
GRATZER, WB
GRATZER, WB
中科院分区:
医学4区
文献类型:
--
作者:
DLUZEWSKI, AR;RANGACHARI, K;GRATZER, WB

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恶性疟原虫对人红细胞的侵袭可被蛋白酶抑制剂亮抑酶肽和凝乳酶抑制素抑制。如果先用胰凝乳蛋白酶处理细胞,则胰凝乳蛋白酶抑制剂的效力降低。另一方面,新鲜细胞在再侵袭阶段暴露于同步培养物的上清液没有显示出这种效果。这表明,蛋白水解步骤发生在入侵的过程中,并可能局限于入侵的寄生虫和红细胞之间的接触区域。为了测试这一点,将亮抑酶肽或凝乳酶抑制素引入裂解的细胞中,然后将其重新密封。细胞内抑制剂强烈降低侵袭。亮抑酶肽还对寄生虫滋养体阶段的发育产生了显著影响:寄生虫内发育出一个巨大的空泡,显然含有未消化的血红蛋白。这并没有完全停止发育,空泡化的寄生虫可以通过用皂苷裂解寄生的宿主细胞以相对纯的形式回收。
Invasion of human red blood cells by Plasmodium falciparum is inhibited by the protease inhibitors, leupeptin and chymostatin. The efficacy of chymostatin was reduced if the cells were first treated with chymotrypsin. On the other hand, exposure of fresh cells to the supernatant from a synchronous culture at the reinvasion stage showed no such effect. This suggests that a proteolytic step occurs in the course of invasion and may be confined to the region of contact between the invading parasite and the erythrocyte. To test this, leupeptin or chymostatin was introduced into lysed cells, which were then resealed. The intracellular inhibitor strongly reduced invasion. Leupeptin also caused a striking effect on the development of the trophozoite stage of the parasite: a massive vacuole, apparently containing undigested haemoglobin, developed within the parasite. This did not totally stop development and the vacuolated parasites could be recovered in relatively pure form by lysis of the parasitized host cells with saponin.