Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
Int J Mol Med. 2022 May;49(5). doi: 10.3892/ijmm.2022.5120. Epub 2022 Mar 16.
Anti‑β‑glycoprotein I (anti‑βGPI) is an anti‑phospholipid antibody that specifically binds to βGPI. 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‑βGPI 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‑βGPI/βGPI is able to induce neutrophil pyroptosis, thereby driving these cells to release IL‑1β 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‑βGPI/βGPI‑induced neutrophil pyroptosis. These pyroptotic neutrophils were also observed to release large amounts of high mobility group box protein 1, which, together with IL‑1β, 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‑βGPI antibody‑associated CI.
抗β糖蛋白 I（anti-βGPI）是一种抗磷脂抗体，特异性结合于βGPI。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 CI 患者的血清抗-βGPI 水平显著升高，中性粒细胞内 NLR 家族富含吡啶结构域蛋白 3（NLRP3）的表达增加，表明炎症细胞死亡在这种病理情况下可能发挥作用。具体而言，确定抗-βGPI/βGPI 能够诱导中性粒细胞细胞焦亡，从而通过细胞表面 Toll 样受体 4 表达调控的途径促使这些细胞释放 IL-1β。在机制水平上，双链 RNA 依赖性蛋白激酶/p38MAPK/NLRP3 途径被表明可以调控抗-βGPI/βGPI 诱导的中性粒细胞细胞焦亡。这些发生细胞焦亡的中性粒细胞还被观察到大量释放高迁移率族蛋白 1，其与 IL-1β 一起促进内皮细胞中 IL-8 和细胞间黏附分子-1 的上调。总之，这些数据表明抑制中性粒细胞细胞焦亡可能是治疗抗-βGPI 抗体相关 CI 的一种可行方法。
