FIGURE 1.

Schematic outline for the role of neutrophils in APAP‐induced ALI. DAMPs like HMGB1 and ATP are released from damaged hepatocytes, recognized by RAGE, P2Y2 receptors, respectively, inducing the activation and recruitment of neutrophils. But the TLR9 expressed on neutrophils recognize mtDNA and then neutrophils could release miR‐223, which inhibits the neutrophil's activation and recruitment. As for other immune cells, they are divided into cells that promote and inhibit the activation and recruitment of neutrophils. Firstly, macrophages express OPN after APAP treatment and then attract neutrophils. Moreover, HMGB1 could recognize TLR4 receptor expressed on macrophages, release IL‐23 to induce the release of IL‐17A in γδ T cells and finally activate and recruit neutrophils. However, Ly6C(hi) monocytes inhibit the activation and recruitment of neutrophils via CCR2 and M‐CSF pathways. Macrophages could also generate MerTK to inhibit neutrophils. Furthermore, TNF‐α/LPS MDSCs could express iNOS to decrease the intrahepatic neutrophils infiltration and induce the apoptosis of activated neutrophil. Activated and recruited neutrophils then migrate to the site of injury to alleviate the inflammation and induce tissue repair. GRPR antagonist could downregulate the expression of CD11b/CD66b via activating MAPKs pathways, which significantly influence the migration of neutrophils to the injury site