Schofield L, Hackett F
National Institute for Medical Research, London, United Kingdom.
J Exp Med. 1993 Jan 1;177(1):145-53. doi: 10.1084/jem.177.1.145.
In this study, we have identified a dominant glycolipid toxin of Plasmodium falciparum. It is a glycosylphosphatidylinositol (GPI). The parasite GPI moiety, free or associated with protein, induces tumor necrosis factor and interleukin 1 production by macrophages and regulates glucose metabolism in adipocytes. Deacylation with specific phospholipases abolishes cytokine induction, as do inhibitors of protein kinase C. When administered to mice in vivo the parasite GPI induces cytokine release, a transient pyrexia, and hypoglycemia. When administered with sensitizing agents it can elicit a profound and lethal cachexia. Thus, the GPI of Plasmodium is a potent glycolipid toxin that may be responsible for a novel pathogenic process, exerting pleiotropic effects on a variety of host cells by substituting for the endogenous GPI-based second messenger/signal transduction pathways. Antibody to the GPI inhibits these toxic activities, suggesting a rational basis for the development of an antiglycolipid vaccine against malaria.
在本研究中，我们鉴定出了恶性疟原虫的一种主要糖脂毒素。它是一种糖基磷脂酰肌醇（GPI）。该寄生虫的GPI部分，无论是游离的还是与蛋白质结合的，均可诱导巨噬细胞产生肿瘤坏死因子和白细胞介素1，并调节脂肪细胞中的葡萄糖代谢。用特定磷脂酶进行脱酰作用可消除细胞因子诱导，蛋白激酶C抑制剂也有同样效果。当在体内给予小鼠时，寄生虫GPI会诱导细胞因子释放、短暂发热和低血糖。当与致敏剂一起给予时，它可引发严重且致命的恶病质。因此，疟原虫的GPI是一种强效糖脂毒素，可能参与了一种新的致病过程，通过替代内源性基于GPI的第二信使/信号转导途径，对多种宿主细胞产生多效性作用。针对GPI的抗体可抑制这些毒性活性，这为开发抗疟疾糖脂疫苗提供了合理依据。
