Tachado S D, Schofield L
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Biochem Biophys Res Commun. 1994 Dec 15;205(2):984-91. doi: 10.1006/bbrc.1994.2763.
A purified, structurally defined glycosylphosphatidylinositol (GPI) derived from the Variant Surface Glycoprotein (VSG) of Trypanosoma brucei, and its biosynthetic precursor P2, was able at submicromolar concentrations to regulate cytokine expression when added directly as pharmacological agonist to host macrophages, by activation of an endogenous protein tyrosine-kinase (PTK) mediated signal transduction pathway. GPI induces rapid onset tyrosine phosphorylation of multiple intracellular substrates, within minutes of addition to LPS-nonresponsive cells, followed shortly thereafter by IL-1 alpha secretion. The PTK antagonists genistein and tyrphostin inhibit both tyrosylphosphorylation and cytokine expression. A monoclonal antibody to GPI also blocks IL-1 alpha induction by total parasite extracts. Thus, as in malaria infection, GPI may induce the cytokine excess causing certain pathological states associated with trypanosomiasis.
从布氏锥虫的变异表面糖蛋白（VSG）衍生而来的一种纯化的、结构明确的糖基磷脂酰肌醇（GPI）及其生物合成前体P2，当以药理激动剂的形式直接添加到宿主巨噬细胞中时，在亚微摩尔浓度下能够通过激活内源性蛋白酪氨酸激酶（PTK）介导的信号转导途径来调节细胞因子的表达。GPI在添加到对脂多糖无反应的细胞后几分钟内就能诱导多种细胞内底物迅速发生酪氨酸磷酸化，随后不久白细胞介素-1α就会分泌。PTK拮抗剂染料木黄酮和 tyrphostin 可抑制酪氨酸磷酸化和细胞因子表达。一种针对GPI的单克隆抗体也能阻断全寄生虫提取物诱导的白细胞介素-1α。因此，如同在疟疾感染中一样，GPI可能会诱导细胞因子过量，从而导致与锥虫病相关的某些病理状态。
