Neutrophil-macrophage crosstalk network in acute lung injury: feedback circuits linking cytokine storm and cell death

Neutrophils (NE) and macrophages (Mø) are canonical cellular components of the innate immune defense and are involved throughout the course of acute lung injury (ALI). The crosstalk between these two cell types is pivotal for elucidating the complex mechanisms underlying inflammation. This review focuses on the bidirectional interactions between NE and Mø mediated by cytokines and phagocytosis. In addition, emerging concepts, including exosomes and migrasomes, are discussed to further delineate the role of NE in this crosstalk network. Certain pro-inflammatory cytokines amplify inflammation through cascade effects, ultimately leading to a cytokine storm. Pro-inflammatory and anti-inflammatory processes are dynamically coordinated and diverge at key regulatory nodes, forming multiple positive and negative feedback loops that collectively establish the inflammatory network model of ALI. The terminal outcome of this network is cell death, encompassing apoptosis, necroptosis, pyroptosis, and PANoptosis. By integrating the crosstalk network with cell death pathways, a more comprehensive regulatory framework is constructed, enabling an in-depth exploration of the molecular mechanisms underlying ALI.