NMI induces chemokine release and recruits neutrophils through the activation of NF-kappaB pathway

Abstract

Neutrophils are essential components of the innate immune system, playing a pivotal role in immune responses. These cells rapidly migrate to sites of inflammation or tissue injury, facilitating pathogen clearance and tissue repair. The chemotactic signaling network regulating neutrophil recruitment is complex and not fully understood, particularly regarding damage-associated molecular patterns (DAMPs). In our previous research, we identified NMI as a DAMP that activates dendritic cells and macrophages, amplifying inflammatory responses and contributing to both acute and chronic inflammation. In this study, we investigated the role of NMI in neutrophil recruitment. We purified and characterized a recombinant murine NMI protein, ensuring endotoxin removal while preserving biological activity. In vivo experiments demonstrated that NMI enhances neutrophil recruitment in both a murine air pouch model and an acute peritonitis model, mediated by macrophage-derived chemokines. In vitro assays revealed a concentration-dependent increase in neutrophil migration induced by NMI, facilitated by chemokine secretion and subsequent migration through the CXCR2 receptor. Importantly, we established that NMI activates chemokine expression via the NF-kappaB signaling pathway. These findings provide insights into the mechanisms of NMI-induced neutrophil migration, enhancing our understanding of neutrophil recruitment during inflammation.