Andrews N W, Abrams C K, Slatin S L, Griffiths G
Department of Pathology, Kaplan Cancer Center, New York University Medical Center, New York 10016.
Cell. 1990 Jun 29;61(7):1277-87. doi: 10.1016/0092-8674(90)90692-8.
Protozoan parasite T. cruzi invades cells within acidic vacuoles, but shortly afterward escapes into the cytosol. Exit from the phagosome is blocked by raising the pH of acidic compartments, suggesting that a previously described acid-active hemolysin secreted by T. cruzi might be involved in the membrane disruption process. Here we show that T. cruzi supernatants are cytotoxic for nucleated cells at pH 5.5 and contain a protein reactive with antibodies against reduced and alkylated human C9 (the ninth component of complement). The C9 cross-reactive protein (TC-TOX) copurified with the cytolytic activity, and the active fractions induced conductance steps characteristic of transmembrane ion channels in planar phospholipid bilayers. Immunocytochemical studies using antibodies against purified TC-TOX showed that the protein was localized to the luminal space of parasite-containing phagosomes. We postulate that TC-TOX, when secreted into the acidic environment of the phagosome, forms pores in the membrane, which contribute to its disruption.
原生动物寄生虫克氏锥虫侵入酸性液泡内的细胞，但不久后便逃逸到细胞质中。通过提高酸性区室的pH值可阻止其从吞噬体中逸出，这表明克氏锥虫先前描述的一种酸活性溶血素可能参与了膜破坏过程。在此我们表明，克氏锥虫的上清液在pH 5.5时对有核细胞具有细胞毒性，并且含有一种可与抗还原和烷基化人C9（补体第九成分）抗体发生反应的蛋白质。C9交叉反应蛋白（TC-TOX）与溶细胞活性共同纯化，活性组分在平面磷脂双分子层中诱导出跨膜离子通道特有的电导步骤。使用抗纯化TC-TOX抗体进行的免疫细胞化学研究表明，该蛋白定位于含有寄生虫的吞噬体的腔隙空间。我们推测，TC-TOX分泌到吞噬体的酸性环境中时，会在膜上形成孔道，这有助于膜的破坏。
