早至在20世紀(jì)40年代,，研究人員已就注意到,，被稱作血紅蛋白S（或稱鐮狀細(xì)胞特質(zhì)）的突變血型在某些似乎能夠在瘧疾中存活下來(lái)的非洲人群中尤其普遍,。 如今,，研究人員終于發(fā)現(xiàn)了這種血紅蛋白S的血型以及另外一種叫做血紅蛋白C的突變血型是如何能夠保護(hù)人們免于罹患與嚴(yán)重的瘧疾有關(guān)的疾病和死亡。
據(jù)Marek Cyrklaff及其同事披露,，引起人類(lèi)瘧疾的寄生蟲(chóng)惡性瘧原蟲(chóng)通常在居住于這些細(xì)胞內(nèi)時(shí)為了給自己制造一種細(xì)胞骨架而會(huì)從紅細(xì)胞中“采挖”一種叫做肌動(dòng)蛋白的蛋白質(zhì),。
然而，隨著時(shí)間的推進(jìn)而演變出含有血紅蛋白S或血紅蛋白C這兩種異常血細(xì)胞結(jié)構(gòu)的紅血球看來(lái)能夠限制這種寄生蟲(chóng)構(gòu)建這種細(xì)胞骨架的能力,。 研究人員應(yīng)用低溫電子斷層掃描技術(shù)發(fā)現(xiàn),，惡性瘧原蟲(chóng)會(huì)收獲在正常紅細(xì)胞中可見(jiàn)的肌動(dòng)蛋白來(lái)構(gòu)建其細(xì)胞骨架并強(qiáng)化其毛雷爾氏裂口，后者會(huì)將該虐原蟲(chóng)的蛋白轉(zhuǎn)移到紅細(xì)胞的表面,。
Cyrklaff 及其他的研究人員接著觀察到,，在那些含有血紅蛋白S或血紅蛋白C的紅細(xì)胞中，該瘧原蟲(chóng)的細(xì)胞骨架及其毛雷爾氏裂口已被削弱,。
鑒于他們的發(fā)現(xiàn),，研究人員提出，這兩種突變的血細(xì)胞結(jié)構(gòu)扮演了一種抵抗瘧疾的保護(hù)性作用,，而在正常血細(xì)胞中干擾肌動(dòng)蛋白的重構(gòu)可能代表了一種針對(duì)某些類(lèi)型病原體的新的防御機(jī)制,。(生物谷 Bioon.com)
doi:10.1126/science.1213775
PMC:
PMID:
Hemoglobins S and C Interfere with Actin Remodeling in Plasmodium falciparum–Infected Erythrocytes
Marek Cyrklaff, Cecilia P. Sanchez, Nicole Kilian, Cyrille Bisseye, Jacques Simpore, Friedrich Frischknecht, Michael Lanzer
The hemoglobins S and C protect carriers from severe Plasmodium falciparum malaria. Here, we found that these hemoglobinopathies affected the trafficking system that directs parasite-encoded proteins to the surface of infected erythrocytes. Cryoelectron tomography revealed that the parasite generated a host-derived actin cytoskeleton within the cytoplasm of wild-type red cells that connected the Maurer's clefts with the host cell membrane and to which transport vesicles were attached. The actin cytoskeleton and the Maurer's clefts were aberrant in erythrocytes containing hemoglobin S or C. Hemoglobin oxidation products, enriched in hemoglobin S and C erythrocytes, inhibited actin polymerization in vitro and may account for the protective role in malaria.
