Coronado Lorena Michelle, Tayler Nicole Michelle, Correa Ricardo, Giovani Rita Marissa, Spadafora Carmenza
Centro de Biología Celular y Molecular de Enfermedades, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), Panama.
J Vis Exp. 2013 Mar 2(73):e50342. doi: 10.3791/50342.
Unlike other Plasmodium species, P. falciparum can be cultured in the lab, which facilitates its study (1). While the parasitemia achieved can reach the ≈40% limit, the investigator usually keeps the percentage at around 10%. In many cases it is necessary to isolate the parasite-containing red blood cells (RBCs) from the uninfected ones, to enrich the culture and proceed with a given experiment. When P. falciparum infects the erythrocyte, the parasite degrades and feeds from haemoglobin (2, 3). However, the parasite must deal with a very toxic iron-containing haem moiety (4, 5). The parasite eludes its toxicity by transforming the haem into an inert crystal polymer called haemozoin (6, 7). This iron-containing molecule is stored in its food vacuole and the metal in it has an oxidative state which differs from the one in haem (8). The ferric state of iron in the haemozoin confers on it a paramagnetic property absent in uninfected erythrocytes. As the invading parasite reaches maturity, the content of haemozoin also increases (9), which bestows even more paramagnetism on the latest stages of P. falciparum inside the erythrocyte. Based on this paramagnetic property, the latest stages of P. falciparum infected-red blood cells can be separated by passing the culture through a column containing magnetic beads. These beads become magnetic when the columns containing them are placed on a magnet holder. Infected RBCs, due to their paramagnetism, will then be trapped inside the column, while the flow-through will contain, for the most part, uninfected erythrocytes and those containing early stages of the parasite. Here, we describe the methodology to enrich the population of late stage parasites with magnetic columns, which maintains good parasite viability (10). After performing this procedure, the unattached culture can be returned to an incubator to allow the remaining parasites to continue growing.
与其他疟原虫物种不同,恶性疟原虫可以在实验室中培养,这便于对其进行研究(1)。虽然所达到的寄生虫血症水平可以达到约40%的极限,但研究人员通常将该百分比保持在10%左右。在许多情况下,有必要从未感染的红细胞中分离出含有寄生虫的红细胞(RBC),以富集培养物并进行特定实验。当恶性疟原虫感染红细胞时,寄生虫会降解并以血红蛋白为食(2,3)。然而,寄生虫必须处理一种毒性很强的含铁血红素部分(4,5)。寄生虫通过将血红素转化为一种称为疟色素的惰性晶体聚合物来规避其毒性(6,7)。这种含铁分子储存在其食物泡中,其中的金属具有与血红素中不同的氧化态(8)。疟色素中铁的三价状态赋予其一种未感染红细胞所没有的顺磁性。随着入侵的寄生虫成熟,疟色素的含量也会增加(9),这赋予了红细胞内恶性疟原虫最新阶段更多的顺磁性。基于这种顺磁性,可以通过将培养物通过装有磁珠的柱子来分离恶性疟原虫感染红细胞的最新阶段。当装有磁珠的柱子放置在磁架上时,这些磁珠会产生磁性。由于其顺磁性,感染的红细胞随后会被困在柱子内,而流出物在很大程度上会包含未感染的红细胞和含有寄生虫早期阶段的红细胞。在这里,我们描述了一种使用磁柱富集晚期寄生虫群体的方法,该方法能保持良好的寄生虫活力(10)。执行此程序后,未附着的培养物可以放回培养箱中,以使剩余的寄生虫继续生长。