Cytoadherence by Plasmodium falciparum-infected erythrocytes is correlated with the expression of a family of variable proteins on infected erythrocytes.
Cytoadherence by Plasmodium falciparum-infected erythrocytes is correlated with the expression of a family of variable proteins on infected erythrocytes.
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DOI：
10.1084/jem.168.4.1307
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发表时间：
1988-10-01
期刊：
影响因子：
--
通讯作者：
Leech J
中科院分区：
文献类型：
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作者：
Magowan C;Wollish W;Anderson L;Leech J
恶性疟原虫感染的红细胞(IRBCs)特异性地附着于静脉内皮细胞，从而逃避脾依赖的免疫机制。我们研究了细胞黏附的分子基础。我们在这里报道，IRBCs的细胞黏附能力与IRBCs表面一系列可变蛋白的表达有关。这些研究的关键是使用体外技术来调节克隆寄生虫的细胞黏附表型。在最初的研究中，我们发现培养适应的寄生虫对细胞的粘附性很差或不粘附性。为了筛选细胞贴壁的寄生虫，我们将打结的IRBCs与C32黑色素瘤细胞孵育并培养贴壁细胞。反复选择产生的寄生虫具有更高的细胞粘附性。为了筛选非细胞黏附性寄生虫，我们培养了不黏附于C32黑色素瘤细胞的细胞。来自两个不同克隆分离株的细胞贴壁IRBCs具有较大的(MR大于2.4×10(5))放射性碘化蛋白，不同分离株之间大小不同，但具有与Triton X-100相同的胰酶敏感性和不溶性的生化特性。在未感染的红细胞中没有检测到这些蛋白，这表明它们是寄生虫确定的，也不能在含有寄生虫的IRBCs中检测到它们，这些IRBCs在未经选择的情况下培养了数月。随着对细胞黏附表型的持续选择，出现了更多分子尺寸更大的IRBC表面蛋白(MR为2.9×10(5)和3.2×10(5))。克隆寄生虫细胞黏附表型的一系列可逆变化伴随着IRBC表面蛋白分子大小的变化。细胞黏附增加与较大蛋白质的表达相关，细胞黏附减少与较小蛋白质的表达相关；与IRBC膜相关的另外两种寄生虫蛋白质的分子大小没有变化。结果表明，该蛋白家族的表达与寄生虫的细胞黏附表型密切相关，提示该家族的成员在介导IRBCs与内皮细胞之间的黏附中起着重要作用。
Plasmodium falciparum-infected erythrocytes (IRBCs) adhere specifically to venular endothelium and thereby evade spleen-dependent immune mechanisms. We have investigated the molecular basis of cytoadherence. We report here that the capacity for cytoadherence of IRBCs is correlated with the expression of a family of variable proteins on the surface of IRBCs. Essential to these studies was the use of in vitro techniques for modulating the cytoadherence phenotype of cloned parasites. In initial studies, we found culture-adapted parasites to be poorly cytoadherent or noncytoadherent. To select for cytoadherent parasites, we incubated knobbed IRBCs with C32 melanoma cells and cultured the adherent cells. Repeated rounds of selection produced parasites with increased cytoadherence. To select for noncytoadherent parasites, we cultured the cells that did not adhere to C32 melanoma cells. Cytoadherent IRBCs from two different cloned isolates had large (Mr greater than 2.4 x 10(5) radioiodinatable proteins that differed in size between the isolates but had in common the biochemical properties of trypsin sensitivity and insolubility with Triton X-100. The proteins were not detected with uninfected erythrocytes, indicating that they were parasite determined, nor were they detected with IRBCs containing parasites cultured for many months without selection. With continued selection for the cytoadherent phenotype, additional IRBC surface proteins with larger molecular sizes (Mr 2.9 x 10(5) and 3.2 x 10(5] appeared. A sequence of reversible changes in the cytoadherence phenotype of cloned parasites was accompanied by variation in the molecular size of the IRBC surface protein. Increased cytoadherence was correlated with expression of larger proteins and decreased cytoadherence was correlated with expression of smaller proteins; there was no change in the molecular size of two other parasite proteins associated with the IRBC membrane. The results indicate that the expression of this family of proteins is closely linked to the cytoadherence phenotype of the parasites, suggesting that the members of the protein family have a role in mediating cytoadherence between IRBCs and endothelial cells.