Resistance of paroxysmal nocturnal hemoglobinuria cells to the glycosylphosphatidylinositol-binding toxin aerolysin.
Resistance of paroxysmal nocturnal hemoglobinuria cells to the glycosylphosphatidylinositol-binding toxin aerolysin.
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DOI：
10.1182/blood.v93.5.1749
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发表时间：
1999-03
期刊：
影响因子：
20.3
通讯作者：
R. Brodsky;G. Mukhina;K. Nelson;Tracy S. Lawrence;Richard J. Jones;J. Buckley
中科院分区：
文献类型：
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作者：
R. Brodsky;G. Mukhina;K. Nelson;Tracy S. Lawrence;Richard J. Jones;J. Buckley
阵发性睡眠性血红蛋白尿症（PNH）是由PIGA基因体细胞突变引起的克隆性干细胞疾病。该基因的产物是合成糖基磷脂酰肌醇（GPI）锚所必需的;因此，PNH细胞的表型标志是所有GPI锚定蛋白的缺失或明显缺乏。气溶素是由细菌病原体嗜水气单胞菌分泌的毒素，并且能够通过在结合GPI锚定受体后在靶细胞的膜中形成通道来杀死靶细胞。我们发现，PNH血细胞（红细胞、淋巴细胞和粒细胞），而不是来自正常或其他血液疾病的血细胞，对气单胞菌溶素的细胞毒性作用有抵抗力。气溶素暴露后PNH细胞的裂解百分比与通过流式细胞术测量的样品中的CD 59（+）细胞的百分比一致。红细胞溶解动力学与PNH红细胞类型相关。PNH III型细胞完全耐气溶素，而PNH II型细胞显示中间的敏感性。重要的是，气溶素的使用使我们能够检测PNH群体，不能通过标准流式细胞术检测。PNH细胞对气溶素的抗性允许用于PNH的简单、廉价的测定，其是敏感的和特异的。气溶素在研究PNH生物学方面也是有用的。
Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal stem cell disorder caused by a somatic mutation of the PIGA gene. The product of this gene is required for the biosynthesis of glycosylphosphatidylinositol (GPI) anchors; therefore, the phenotypic hallmark of PNH cells is an absence or marked deficiency of all GPI-anchored proteins. Aerolysin is a toxin secreted by the bacterial pathogen Aeromonas hydrophila and is capable of killing target cells by forming channels in their membranes after binding to GPI-anchored receptors. We found that PNH blood cells (erythrocytes, lymphocytes, and granulocytes), but not blood cells from normals or other hematologic disorders, are resistant to the cytotoxic effects of aerolysin. The percentage of lysis of PNH cells after aerolysin exposure paralleled the percentage of CD59(+) cells in the samples measured by flow cytometry. The kinetics of red blood cell lysis correlated with the type of PNH erythrocytes. PNH type III cells were completely resistant to aerolysin, whereas PNH type II cells displayed intermediate sensitivity. Importantly, the use of aerolysin allowed us to detect PNH populations that could not be detected by standard flow cytometry. Resistance of PNH cells to aerolysin allows for a simple, inexpensive assay for PNH that is sensitive and specific. Aerolysin should also be useful in studying PNH biology.