3.2 Immune macrophages
As an important cell of the innate immune system, macrophages can show different phenotypes and functions when stimulated by external factors, and they are widely distributed in various tissues and organs of the body. Among them, M1 macrophages (classically activated macrophages) are activated and secreted proinflammatory cytokines, which play a central role in the host’s defense against infection, while M2 macrophages (alternatively activated macrophages) are involved in the body’s anti-inflammatory response and tissue remodeling response by secreting inhibitory cytokines [29]. Hypoxia-inducible factor-1 in sepsis α、 Abnormal changes in substances such as 5-adenosine monophosphate-activated protein kinase (AMPK) and succinate dehydrogenase can regulate the metabolism of immune macrophages, and then directly affect the prognosis of sepsis [30]. A recent study by Kong [31] et al. Showed that the aerobic glycolysis of macrophages could be regulated by targeting GAPDH (a rate-limiting enzyme that regulates the rate of aerobic glycolysis), thereby inhibiting the activation of inflammatory macrophages to play an anti-inflammatory role, and significantly reducing the mortality of septic rats. In addition, inhibiting the abnormal activation of macrophages can regulate the polarization phenotype of macrophages, promote tissue repair and angiogenesis, inhibit pro-inflammatory immune response, and reduce tissue and organ damage. There is evidence that[32], macrophages regulate tissue damage and affect the inflammatory response in the microenvironment, which is related to the release of lipid bilayer-blocking structure (EV). In addition, damaged tissue cells can release ev to activate local macrophages to promote tissue repair.