A role for lipid rafts in C1q-triggered O2- generation by human neutrophils.
A role for lipid rafts in C1q-triggered O2- generation by human neutrophils.
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DOI：
10.1016/j.molimm.2004.03.029
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发表时间：
2004-06
影响因子：
3.6
通讯作者：
Iyore Otabor;S. Tyagi;F. Beurskens;I. Ghiran;P. Schwab;A. Nicholson‐Weller;L. Klickstein
中科院分区：
文献类型：
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作者：
Iyore Otabor;S. Tyagi;F. Beurskens;I. Ghiran;P. Schwab;A. Nicholson‐Weller;L. Klickstein
钙网蛋白，一个候选的C1 q受体，最近被证明是目前在人类中性粒细胞表面与糖基磷脂酰肌醇（GPI）锚定蛋白，特别是CD 59。在这项研究中，我们发现CD 59抗体以及其他测试的GPI锚定蛋白抗体抑制了C1 q触发的PMN释放O2−。甲基β环糊精（MβCD）处理细胞以破坏脂筏也阻止了C1 q触发的O2−产生。中性粒细胞产生O2-需要β 2整合素依赖性共刺激，但MβCD对LFA-1或Mac-1介导的粘附、可溶性iC 3b与中性粒细胞的结合或扩散和迁移没有影响，所有这些都表明中性粒细胞整合素功能保持完整。经MβCD处理的PMN的流式细胞术分析显示，PMN颗粒相关整合素表达上调，整合素激活报告表位相应增加，而GPI锚定抗原表达降低。这些数据支持了一个模型，其中脂筏及其相关的GPI锚定蛋白对于C1 q触发的O2−产生至关重要，这与钙网蛋白作为PMN产生O2−的C1 q受体的模型一致。
Calreticulin, a candidate C1q receptor, was shown recently to be present on the surface of human neutrophils in association with glycosylphosphatidylinositol (GPI) anchored proteins, particularly CD59. In this study, we show that antibodies to CD59, as well as to every other GPI-anchored protein tested, inhibited the C1q-triggered release of O2−from PMN. Methyl β cyclodextrin (MβCD) treatment of the cells to disrupt lipid rafts also prevented C1q-triggered O2−production. β2integrin-dependent co-stimulation is required for O2−production from PMN, however MβCD had no effect on LFA-1 or Mac-1-mediated adhesion, soluble iC3b binding to PMN, or spreading and migration, all of which suggested that PMN integrin function remained intact. Flow cytometric analysis of PMN treated with MβCD showed upregulation of PMN granule-associated integrins and a corresponding increase in integrin activation-reporter epitopes, in contrast to the decreased expression of GPI-anchored antigens. These data support a model where lipid rafts and their associated GPI-anchored proteins are critical for C1q-triggered O2−production, consistent with a model where calreticulin serves as the C1q receptor for O2−production from PMN.