Abstract
Platelet microparticles (PMPs) are vesicles that are released by platelets into the extracellular space and play a role in antiphospholipid antibody syndromes. PMPs have recently been recognized as a new and viable cell. There is growing evidence that the anti-β2 glycoprotein (GPI)/β2GPI complex is associated with aberrant activation of PMPs. Although studies suggest that aberrant activation of PMPs may lead to inflammatory necrosis of endothelial cells, the underlying mechanisms remain unclear. We found that although the difference in the number of PMPs was not statistically significant, NLR family pyrin domain containing 3 (NLRP3) within PMPs was increased during stimulation of anti-β2GPI/β2GPI complexes. Furthermore, we demonstrated that anti-β2GPI/β2GPI complex-induced PMPs effectively stimulated endothelial cell pyroptosis via the NLRP3/nuclear factor (NF)-κB/gasdermin D (GSDMD) signaling pathway as well as the NLRP3/Caspase-1 signaling pathway. Additionally, inhibition of NLRP3 expression in PMPs effectively reduced the inflammatory response and pyroptosis in endothelial cells. Our data suggest that PMPs aberrantly activated by anti-β2GPI/β2GPI complexes play a vital role in endothelial cell pyroptosis, and these studies provide major insights into the mechanisms of thrombosis during the treatment of antiphospholipid antibody syndrome.