Cell surface glycosaminoglycans are not obligatory for Plasmodium berghei sporozoite invasion in vitro
Cell surface glycosaminoglycans are not obligatory for Plasmodium berghei sporozoite invasion in vitro
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DOI：
10.1016/0166-6851(95)02563-4
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发表时间：
1996-02-01
影响因子：
1.5
通讯作者：
Nussenzweig, V
中科院分区：
文献类型：
--
作者：
Frevert, U;Sinnis, P;Nussenzweig, V
疟疾环子孢子（CS）蛋白结合的糖胺聚糖链硫酸乙酰肝素蛋白聚糖存在于肝细胞和肝癌细胞的基底外侧表面在体外。当注射到小鼠体内时，CS蛋白被肝细胞从血液循环中迅速清除。HSPG的结合区域是CS蛋白进化上保守的II+区。在这里，我们已经问是否存在的糖胺聚糖的靶细胞的质膜上的子孢子在体外入侵所需的。使用两种类型的靶细胞：HepG 2细胞，其允许伯氏疟原虫子孢子发育成成熟的外红细胞形式，和CHO细胞，其中寄生虫的细胞内发育在穿透后早期被阻止。与CHO-K1细胞的侵袭相比，表达低硫酸化糖胺聚糖或不表达糖胺聚糖的突变CHO细胞的侵袭分别仅被抑制41-49%或24- 32%。先前用肝素酶或肝素酶切割HepG 2表面膜糖胺聚糖对这些细胞中随后的伯氏疟原虫子孢子侵入和EEF发育没有显著的抑制作用，尽管糖胺聚糖裂解酶处理从细胞表面去除了超过80%的CS结合位点。这些结果表明，虽然靶细胞表面上的糖胺聚糖的存在下，增强子孢子的入侵，糖胺聚糖是不需要的子孢子穿透或体外红细胞外形式的发展。
The malaria circumsporozoite (CS) protein binds to glycosaminoglycan chains from heparan sulfate proteoglycans present on the basolateral surface of hepatocytes and hepatoma cells in vitro. When injected into mice, CS protein is rapidly cleared from the blood circulation by hepatocytes. The binding region for the HSPGs is the evolutionarily conserved region II-plus of the CS protein. Here we have asked whether the presence of glycosaminoglycans on the plasma membrane of target cells is required for sporozoite invasion in vitro. Two types of target cells were used: HepG2 cells, which are permissive for Plasmodium berghei sporozoite development into mature exoerythrocytic forms, and CHO cells, in which the intracellular development of the parasites is arrested early after penetration. The invasion of mutant CHO cells expressing undersulfated glycosaminoglycans or no glycosaminoglycans was only inhibited 41-49% or 24-32%, respectively, in comparison to invasion of CHO-K1 cells. Previous cleavage of HepG2 surface membrane glycosaminoglycans with heparinase or heparitinase had no significant inhibitory effect on subsequent P. berghei sporozoite invasion and EEF development in these cells, although the glycosaminoglycan lyase treatments removed over 80% of CS binding sites from the cell surface. These results suggest that although the presence of glycosaminoglycans on the target cell surface enhances sporozoite invasion, glycosaminoglycans are not required for sporozoite penetration or the development of exoerythrocytic forms in vitro.