Anti-β2GPI/β2GPI induces neutrophil pyroptosis and thereby enhances ICAM-1 and IL-8 expression in endothelial cells
Anti-β2GPI/β2GPI induces neutrophil pyroptosis and thereby enhances ICAM-1 and IL-8 expression in endothelial cells
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DOI：
10.3892/ijmm.2022.5120
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发表时间：
2022-05-01
影响因子：
5.4
通讯作者：
Liu, Yanhong
中科院分区：
文献类型：
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作者：
Luo, Jie;Zhang, Mengyu;Liu, Yanhong
抗β（2）-糖蛋白I（抗β（2）GPI）是一种特异性结合β（2）GPI的抗磷脂抗体。越来越多的证据表明，这种自身抗体与特定的血栓形成条件密切相关。脑梗死（CI）是一种与高发病率和死亡率相关的血栓形成形式。在本研究中，确定了CI患者表现出显著增加的血清抗β（2）GPI水平以及中性粒细胞内增加的NLR家族pyrin结构域3（NLRP 3）表达，表明在这种病理背景下炎性细胞死亡的潜在作用。具体地，确定了抗β（2）GPI/β（2）GPI能够诱导嗜中性粒细胞焦亡，从而驱动这些细胞通过由细胞表面Toll样受体4表达调节的途径释放IL-1 β。在机制水平上，双链RNA依赖性蛋白激酶/p38 MAPK/NLRP 3通路被证明控制抗β 2 GPI/β 2 GPI诱导的中性粒细胞焦亡。还观察到这些致炎性中性粒细胞释放大量高迁移率族蛋白1，其与IL-1 β一起促进内皮细胞中的IL-8和细胞间细胞粘附分子-1上调。总之，这些数据表明，抑制嗜中性粒细胞焦亡可能代表治疗抗β（2）GPI抗体相关CI的可行方法。
Anti-beta(2)-glycoprotein I (anti-beta(2)GPI) is an anti-phospholipid antibody that specifically binds to beta(2)GPI. There is growing evidence that this autoantibody is closely linked to specific thrombotic conditions. Cerebral infarction (CI) is a form of thrombosis associated with high rates of morbidity and mortality. In the present study, it was determined that patients with CI exhibited significantly increased serum anti-beta(2)GPI levels as well as increased NLR family pyrin domain containing 3 (NLRP3) expression within neutrophils, suggesting a potential role for inflammatory cell death in this pathological context. Specifically, it was determined that anti-beta(2)GPI/beta(2)GPI is able to induce neutrophil pyroptosis, thereby driving these cells to release IL-1 beta via a pathway regulated by cell surface Toll-like receptor 4 expression. At the mechanistic level, the double-stranded RNA-dependent protein kinase/p38MAPK/NLRP3 pathway was indicated to govern anti-beta(2)GPI/beta(2)GPI-induced neutrophil pyroptosis. These pyroptotic neutrophils were also observed to release large amounts of high mobility group box protein 1, which, together with IL-1 beta, promoted IL-8 and intercellular cell adhesion molecule-1 upregulation in endothelial cells. In summary, these data suggest that inhibiting neutrophil pyroptosis may represent a viable approach to treating anti-beta(2)GPI anti- body-associated CI.