Anti‑βGPI/βGPI induces neutrophil pyroptosis and thereby enhances ICAM‑1 and IL‑8 expression in endothelial cells.

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.