Stimulation of eryptosis by anti-a lgG antibodies
Stimulation of eryptosis by anti-a lgG antibodies
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DOI：
10.1159/000107542
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发表时间：
2007-01-01
影响因子：
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通讯作者：
Lang, Florian
中科院分区：
文献类型：
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作者：
Attanasio, Philipp;Shumilina, Ekaterina;Lang, Florian
抗A IgG抗体先前已显示刺激Ca 2+进入红细胞。胞质游离Ca 2+浓度的增加已知会触发红细胞凋亡，即。e.自杀性红细胞死亡，特征为红细胞表面磷脂酰丝氨酸暴露。由于巨噬细胞配备有磷脂酰丝氨酸受体，它们结合、吞噬和降解暴露于磷脂酰丝氨酸的细胞。进行本实验以探索抗A IgG是否触发红细胞的磷脂酰丝氨酸暴露。磷脂酰丝氨酸的暴露量是从膜联蛋白- V的结合来估计的，如在流式细胞仪分析中所测定的.暴露于抗A IgG（0.5 μ g/ ml）确实显著增加了A血型红细胞中的膜联蛋白- V结合，但在0血型红细胞中没有. Fluo 3荧光显示，抗A IgG可增加胞浆Ca ~（2+）浓度。全细胞膜片钳记录揭示了用抗-A-IgG处理后Ca 2 +-渗透性阳离子通道的激活。膜联蛋白- V结合抗- A IgG暴露后钝化钙离子去除，而抗- A IgG刺激的阳离子通道活性不依赖于细胞外钙离子。渗透性休克（红细胞暴露于850 mOsm）增加膜联蛋白结合，暴露于抗A IgG进一步增强了这种作用。总之，抗A IgG激活红细胞阳离子通道，导致Ca 2+进入和随后的红细胞膜混乱。该效应很可能有助于在针对A抗原的免疫反应后消除红细胞。
Anti- A IgG antibodies have previously been shown to stimulate Ca2+ entry into red blood cells. Increased cytosolic free Ca2+ concentration is known to trigger eryptosis, i. e. suicidal erythrocyte death, characterized by exposure of phosphatidylserine at the erythrocyte surface. As macrophages are equipped with phosphatidylserine receptors, they bind, engulf and degrade phosphatidylserine exposing cells. The present experiments have been performed to explore whether anti- A IgGs trigger phosphatidylserine exposure of erythrocytes. Phosphatidylserine exposure was estimated from annexin- V binding as determined in FACS analysis. Exposure to anti- A IgGs ( 0.5 mu g/ ml) indeed significantly increased annexin- V binding in erythrocytes with blood group A, but not in erythrocytes with blood group 0. According to Fluo3 fluorescence, anti- A IgGs increased cytosolic Ca2+ concentration. Whole cell patch clamp recordings revealed the activation of a Ca2+- permeable cation channel following treatment with anti- A- IgGs. Annexin- V binding following anti- A IgG exposure was blunted by Ca2+ removal while anti- A IgG- stimulated cation channel activity was not dependent on extracellular Ca2+. Osmotic shock ( exposure of erythrocytes to 850 mOsm) increased annexin binding, an effect further enhanced by exposure to anti- A IgGs. In conclusion, anti- A IgGs activate erythrocyte cation channels leading to Ca2+ entry and subsequent erythrocyte cell membrane scrambling. The effect most likely contributes to the elimination of erythrocytes following an immune reaction against the A antigen.