Bactericidal activity of transendothelial neutrophils based the endothelial IL-1α crosstalk during neutrophil–endothelial interaction

Abstract

Abstract Neutrophils across endothelial cells to capture and eliminate bacterial pathogens is served as a vocation to prevent infectious diseases during innate immune. However, the mechanisms behind neutrophil-endothelial interaction on the bacterial elimination remains unclear. In this study, we employed a transwell system to co-culture rat intestinal mucosa microvascular endothelial cells (RIMVECs) and neutrophils to illustrate the killing mechanisms of transendothelial neutrophils. We discovered that endothelial interleukin-1α (IL-1α) promoted the survival of rats under Escherichia coli infection. IL-1α enhanced the bactericidal activity of transendothelial neutrophils, while the release of IL-1α is inhibited by lipopolysaccharide (LPS) derived from E. coli during infectious process. In addition, LPS majority damaged RIMVECs on cell membrane and induced cell necrosis. LPS promoted E. coli to escape from neutrophils in vivo and in vitro. Though the isobaric tags for relative and absolute quantification (iTRAQ) method to identify differentially expressed proteins of RIMVECs, we found that IL-1α modulates RIMVECs occurred on the plasma membrane, endoplasmic reticulum and mitochondrial envelope. There were eleven common proteins to persist regulatory. 2 h treatment of IL-1α triggered the cell adhesion molecules (CAMs) of RIMVECs, while oxidative phosphorylation was required for long times’ incubation of IL-1α (4 and 8 h). Our work highlights the critical role of endothelial IL-1α during neutrophil- endothelial interaction, which offered new targets in the bactericidal activity of neutrophils.