NEUTROPHIL ACTIVATION BY ANTI-BETA(2) GLYCOPROTEIN-I MONOCLONAL-ANTIBODIES VIA FC-GAMMA RECEPTOR-II
NEUTROPHIL ACTIVATION BY ANTI-BETA(2) GLYCOPROTEIN-I MONOCLONAL-ANTIBODIES VIA FC-GAMMA RECEPTOR-II
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DOI：
10.1002/jlb.57.3.387
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发表时间：
1995-03-01
影响因子：
5.5
通讯作者：
COLOMB, MG
中科院分区：
文献类型：
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作者：
ARVIEUX, J;JACOB, MC;COLOMB, MG
针对人β（2）-糖蛋白I（β（2）GPI）（一种结合某些抗磷脂抗体所需的血浆蛋白）的鼠单克隆抗体（mAb）已显示具有狼疮抗凝特性并通过Fc γ受体（Fc γ R）交联激活血小板。在这里，我们研究了它们诱导多形核白细胞（PMN）功能反应的能力。测试的6种mAb（IgG 1同种型）与β（2）GPI联合导致人PMN的浓度依赖性活化，如颗粒释放、H2 O2产生和胞质Ca 2+增加所示。这种激活过程伴随着增强中性粒细胞介导的硫酸乙酰肝素从内皮细胞系EA.hy926的损失，而没有细胞溶解或脱离的证据。其中一种mAb的F（ab '）（2）片段以β（2）GPI依赖性方式与PMN结合，但没有激活作用。氨甲酰化β（2）GPI不能介导PMN-抗体结合和随后的激活。此外，与未处理的蛋白质相比，β（2）GPI的阳离子化或其唾液酸基团的去除导致与PMN表面结合并触发激活的效率更高。因此，PMN活化过程取决于mAb通过Fab（通过β（2）GPI）和Fc结构域与这些细胞的结合，这通过用抗Fc γ RII而非抗Fc γ RIII抗体处理后所有应答的抑制得到证实。我们的数据表明，β（2）GPI依赖性抗磷脂抗体的细胞活化模型。
Murine monoclonal antibodies (mAbs) to human beta(2)-glycoprotein I (beta(2)GPI), a plasma protein required for the binding of some antiphospholipid antibodies, have been shown to possess lupus anticoagulant properties and to activate platelets via Fc gamma receptor (Fc gamma R) crosslinking. Here we investigated their ability to induce polymorphonuclear leukocyte (PMN) functional responses. The six mAbs (IgG1) isotype) tested in combination with beta(2)GPI led to a concentration-dependent activation of human PMNs as appreciated by granule release, H2O2 production, and cytosolic Ca2+ increase. This activation process was accompanied by the enhancement of PMN-mediated heparan sulfate loss from the endothelial cell line EA.hy 926 without evidence for cell lysis or detachment. F(ab')(2) fragments of one of the mAbs bound to PMNs in a beta(2)GPI-dependent manner but were devoid of activating effects. Carbamylated beta(2)GPI was unable to mediate PMN-antibody binding and subsequent activation. In addition, cationization of beta(2)GPI or removal of its sialic acid groups led to higher efficiency in binding to the PMN surface and triggering activation in comparison with the untreated protein. Thus, the process of PMN activation depends on mAb binding to these cells through both Fab (via beta(2)GPI) and Fc domains, as confirmed by the suppression of all responses upon treatment with an anti-Fc gamma RII, but not anti-Fc gamma RIII, antibody. Our data suggest a model of cellular activation by beta(2)GPI-dependent antiphospholipid antibodies.