This study reveals a hitherto unknown role of exosomal PGE2 derived from M2 macrophages in increasing 15-LO expression in PMNs, upregulating LXA4 production to downregulate PMN CXCR2 and ROS expressions, inhibiting PMN migration and NET formation, alleviating lung injury, and reducing mortality in sepsis. This evidence concerns the gene CXCR2 and Sepsis.