Abstract
Anti‑β2‑glycoprotein I (anti‑β2GPI) is an anti‑phospholipid antibody that specifically binds to β2GPI. 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‑β2GPI 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‑β2GPI/β2GPI 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‑β2GPI/β2GPI‑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‑β2GPI antibody‑associated CI.