Fig. 1

① I-R injury stimulates the production of LTB4, which binds to BLTR receptors on intravascular neutrophils to induce NE secretion. Neutrophils then transfer NE to EC-JAMC via MAC-1 and hydrolyze it, causing neutrophils at the site of injury to return to the bloodstream through this damaged “gap”. ② In sepsis, CIRP expression is increased and promotes neutrophil producing NE, which subsequently destroys EC-JAMC through the mechanism described in ①. ③ PE2 can signal through the EP4 receptor of macrophages, resulting in increased production of the Alox12 gene, thereby promoting endogenous LXA4 production. LXA4 acts on neutrophils at the injured site and promotes rTEM. ④ Increased neutrophil reverse migration following inhibition of CXCL12/CXCR4 signaling on neutrophils using AMD3100