Shahabuddin M, Fields I, Bulet P, Hoffmann J A, Miller L H
Medical Entomology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Exp Parasitol. 1998 May;89(1):103-12. doi: 10.1006/expr.1998.4212.
We examined several insect antimicrobial peptides to study their effect on Plasmodium gallinaceum zygotes, ookinetes, oocysts, and sporozoites. Only two insect defensins-Aeschna cyanea (dragon fly) and Phormia terranovae (flesh fly)-had a profound toxic effect on the oocysts in Aedes aegypti and on isolated sporozoites. The defensins affected the oocysts in a time-dependent manner. Injecting the peptide into the hemolymph 1 or 2 days after an infectious blood meal had no significant effect on prevalence of infection or relative oocyst density per mosquito. When injected 3 days after parasite ingestion, the relative oocyst density was significantly reduced. Injection on day 4 or later damaged the developing oocysts, although the oocysts density per mosquito was not significantly different when examined on day 8. The oocysts were swollen or had extensive internal vacuolization. The peptides had no detectable effect on the early stages of the parasite: the zygotes and ookinetes tested in vitro. Both the defensins were highly toxic to isolated sporozoites in vitro as indicated by disruption of the membrane permeability barrier, a change in morphology, and loss of motility. In contrast to the toxicity of cecropin and magainin for mosquitoes, defensin, at concentrations that kill parasites, is not toxic to mosquitoes, suggesting that defensin should be studied further as a potential molecule to block sporogonic development of Plasmodium.
我们研究了几种昆虫抗菌肽，以探讨它们对鸡疟原虫合子、动合子、卵囊和子孢子的作用。只有两种昆虫防御素——大蓝蜻蜓（豆娘）和新大陆绿蝇（肉蝇）——对埃及伊蚊体内的卵囊以及分离出的子孢子有显著毒性作用。这些防御素对卵囊的影响具有时间依赖性。在感染性血餐1天或2天后将该肽注入血淋巴，对感染率或每只蚊子的相对卵囊密度没有显著影响。在摄入寄生虫3天后注射，相对卵囊密度显著降低。在第4天或更晚注射会损害发育中的卵囊，尽管在第8天检查时每只蚊子的卵囊密度没有显著差异。卵囊肿胀或有广泛的内部空泡化。这些肽对寄生虫的早期阶段（即体外测试的合子和动合子）没有可检测到的影响。两种防御素在体外对分离出的子孢子都具有高毒性，表现为膜通透性屏障破坏、形态改变和运动能力丧失。与天蚕素和蛙皮素对蚊子的毒性不同，防御素在杀死寄生虫的浓度下对蚊子无毒，这表明防御素作为一种潜在的阻断疟原虫孢子生殖发育的分子值得进一步研究。
