Placenta-derived IL-32β activates neutrophils to promote preeclampsia development

Immune activation at the maternal-fetal interface is a main pathogenic factor of preeclampsia(PE).Neutrophils(PMNs)are activated in PE patients,but the mechanism and consequences of PMN activation need to be further explored.Here,we demonstrated that interleukin-32(IL-32)expression was significantly upregulated in syncytiotrophoblasts(STBs)and that IL-32β was the major isoform with increased expression in the placenta of severe PE(sPE)patients.Furthermore,the level of IL-32 expression in the placenta was correlated with its level in the serum of sPE patients,indicating that IL-32 in the serum is derived mainly from the placenta.Then,in vitro experiments showed that IL-32β could highly activate PMNs and that these IL-32β-activated PMNs were better able to adhere to endothelial cells(HUVECs)and enhance the expression of vascular cell adhesion molecule-1(VCAM-1)and intercellular cell adhesion molecule-1(ICAM-1)in HUVECs,which could be reversed by preincubation with the NADPH oxidase inhibitor VAS 2870.In addition,we showed that IL-32β mainly activated PMNs by binding to proteinase 3.Finally,IL-32β administration induced a PE-like phenotype in a pregnant mouse model.This study provides evidence of the involvement of IL-32β in the pathogenesis of PE.