Sepsis is a life-threatening organ dysfunction caused by a dysfunctional host response to infection. Neutrophils play a protective role by releasing antibacterial proteins or by phagocytizing bacteria. However, excess neutrophils can induce tissue damage. Recently, a novel intercellular communication pathway involving extracellular vesicles (EVs) has garnered considerable attention. However, whether EVs secreted by macrophages mediate neutrophil recruitment to infected sites has yet to be studied. In this study, we assessed the chemotactic effect of EVs isolated from mouse Raw264.7 macrophages on mouse neutrophils and found that CXCL2 was highly expressed in these EVs. By regulating CXCL2 in Raw264.7 macrophages, we found that CXCL2 on macrophage EVs recruited neutrophils in vitro and in vivo. The CXCL2 EVs activated the CXCR2/PKC/NOX4 pathway and induced tissue damage. This study provides information regarding the mechanisms underlying neutrophil recruitment to tissues and proposes innovative strategies and targets for the treatment of sepsis.

脓毒症是一种危及生命的器官功能障碍，由宿主对感染的反应失调引起。中性粒细胞通过释放抗菌蛋白或吞噬细菌发挥保护作用。然而，过量的中性粒细胞会导致组织损伤。最近，一种涉及细胞外囊泡（EV）的新型细胞间通讯途径引起了相当大的关注。然而，巨噬细胞分泌的 EV 是否介导中性粒细胞向感染部位募集还有待研究。在这项研究中，我们评估了从小鼠 Raw264.7 巨噬细胞中分离的 EVs 对小鼠中性粒细胞的趋化作用，发现 CXCL2 在这些 EVs 中高度表达。通过调节 Raw264.7 巨噬细胞中的 CXCL2，我们发现巨噬细胞 EV 上的 CXCL2 在体外和体内募集中性粒细胞。CXCL2 EVs 激活 CXCR2/PKC/NOX4 通路并诱导组织损伤。这项研究提供了有关中性粒细胞向组织募集的机制的信息，并提出了治疗脓毒症的创新策略和目标。