Sieber K P, Huber M, Kaslow D, Banks S M, Torii M, Aikawa M, Miller L H
Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, Maryland 20892.
Exp Parasitol. 1991 Feb;72(2):145-56. doi: 10.1016/0014-4894(91)90132-g.
We studied the point at which a monoclonal antibody (mAb C5) to a surface protein (Pgs25) on Plasmodium gallinaceum ookinetes blocked the infection of Aedes aegypti mosquitoes. The antibody did not block the development of zygotes to ookinetes in vitro. Development of ookinetes to oocysts in the mosquito was blocked to the same extent whether zygotes grew to ookinetes in the presence of mAb C5 or the antibody was added after the ookinetes had reached full development. When ookinetes developed in vitro in the presence of mAb C5, antibody remained on the surface of the parasite for the next 50 hr and did not block attachment to the peritrophic membrane. When ookinetes were fed to mosquitoes, two subpopulations of mosquitoes were observed (high numbers of oocysts per midgut and low numbers of oocysts per midgut). mAb C5 reduced the number of oocysts per midgut in the subpopulation that had low numbers of oocysts. The subpopulation that had high numbers of oocysts was unaffected by antibody, indicating that the antibody did not block invasion of the midgut epithelium. When mAb C5 was fed with gametocytes, the parasites invaded the epithelium at the same time (between 30 and 35 hr after the blood meal) as in controls, although at a markedly reduced rate. The ultrastructural observations were consistent with a block of parasites within the peritrophic membrane and not with a block at the epithelium, as parasites were not seen to accumulate within the space between the peritrophic membrane and the epithelium. The mechanism by which mAb C5 to Pgs25 of P. gallinaceum blocks the penetration of the peritrophic membrane remains undefined. We present evidence that the parasite modifies the peritrophic membrane during penetration, an observation first made for Babesia microti during penetration of the peritrophic membrane in Ixodes ticks. Ookinetes in the absence of antibodies appeared to disrupt the layers of the peritrophic membrane, suggesting an enzymatic mechanism for penetration.
我们研究了一种针对鸡疟原虫动合子表面蛋白（Pgs25）的单克隆抗体（mAb C5）阻断埃及伊蚊感染的作用点。该抗体在体外并不阻断合子发育为动合子。无论合子是在mAb C5存在的情况下发育为动合子，还是在动合子完全发育后再添加该抗体，动合子在蚊子体内发育为卵囊的过程均受到同等程度的阻断。当动合子在mAb C5存在的情况下在体外发育时，抗体在接下来的50小时内仍留在寄生虫表面，且不阻断其与围食膜的附着。当将动合子喂给蚊子时，观察到两类蚊子亚群（每只中肠内卵囊数量多和每只中肠内卵囊数量少）。mAb C5减少了每只中肠内卵囊数量少的亚群中的卵囊数量。每只中肠内卵囊数量多的亚群不受抗体影响，这表明该抗体不阻断中肠上皮的入侵。当mAb C5与配子体一起被投喂时（在血餐后30至35小时之间），寄生虫与对照组一样同时侵入上皮，尽管速率明显降低。超微结构观察结果表明寄生虫在围食膜内受阻，而非在上皮处受阻，因为未观察到寄生虫在围食膜与上皮之间的空间内聚集。针对鸡疟原虫Pgs25的mAb C5阻断围食膜穿透的机制尚不清楚。我们提供的证据表明，寄生虫在穿透过程中会改变围食膜，这一现象最早是在微小巴贝斯虫穿透硬蜱围食膜时观察到的。在没有抗体的情况下，动合子似乎会破坏围食膜的各层结构，这表明存在一种酶促穿透机制。
