Daxing Liu, Department of Cardiovascular Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi Medical University,Zunyi, China; E-mail:
Key words: Macrophages; monocytes; macrophage colonystimulating factor; mononuclear phagocytic system; interleukin-34
After tissue injured, monocytes and macrophages undergo significant phenotypic and functional changes. At the onset of tissue repair, the maintenance and resolution phases play a key role . In a skin model, studies have shown that macrophagedependent iron transporter-mediated iron release is required for hair growth and effective wound healing under steady-state conditions. Which iron transporter deletion will cause iron in macrophages retention is responsible for impaired angiogenesis and stromal cell proliferation, resulting in delayed skin repair. The study found that iron retention in macrophages had no effect on leukocyte recruitment and activation and macrophage polarization. In this study, iron accumulation does not exacerbate the expression of proinflammatory phenotypes in wound healingassociated macrophages . Macrophage dysfunction can lead to abnormal repair, uncontrolled inflammatory mediators and growth factors, as well as the production of anti-inflammatory macrophage defects, resulting in persistent damage, which may eventually lead to the development of pathological fibrosis . Studies have suggested that mononuclear cells and yolk sac-derived tissue macrophages recruited from bone marrow play different roles in different repair stages of some organs. For instance, although genetic results mapping studies have demonstrated that most macrophages in adult hearts are derived from yolk sac and fetal progenitor cells, CCR2 + monocyte-derived macrophages drive early inflammatory responses in heart tissue after injury primary cells . In contrast, embryonic-derived cardiac macrophages are key cells that promote recovery .
Jay and colleagues conducted an exciting study showing that the expression of receptor-inducing macrophages on bone marrow cells 2 is required for the development of Alzheimer’s disease. Inflammation of Ly6c + macrophages highly expresses trigger receptors on bone marrow cells 2, when the trigger receptor activity on bone marrow cells 2 is genetically deleted, the Ly6c + group is virtually eliminated, resulting in reducing inflammation and improving amyloid and tau symptoms. Therefore, expression of a trigger receptor on bone marrow cells 2 has been identified as an important guiding signal in the development of inflammatory macrophages, suggesting that it may represent a therapeutic target in neurodegenerative diseases such as Alzheimer’s disease . Studies have shown that oxidative stress is associated with neurodegenerative diseases such as Alzheimer’s disease. In addition, post-mortem examination of patients with these diseases showed that areas of the brain affected by neuro degeneration showed an increase in the active oxygen index. Macrophages play an important role in inflammation and constitute a major source of reactive oxygen species in the human body. Although reactive oxygen species were previously thought to be produced primarily by tissue macrophages in the brain ie, microglia. Recent reports have indicated the important role of peripheral cells, especially macrophages, suggesting that they are important for the regulation and progression of inflammation .
A particularly important source of reactive oxygen species is activated macrophages, whose increased production may adversely affect the antioxidant-antioxidant balance . In the experiment, acetyl cholinesterase inhibitors used as a standard for the treatment of Alzheimer’s disease showed possible antioxidant activity in macrophages and inhibited the formation of reactive oxygen species, thereby achieving a certain therapeutic effect .
Acute liver failure is one of the rare and life-threatening major diseases that most frequently present in patients without pre-existing liver disease . In the experiment, HepG2 and HL-7702 cells were pretreated with M0, M1 or M2 medium. Hepatocyte apoptosis is then induced by human TNF-α/D-GalN. Exposure of HepG2 cells to M0 medium or M1 medium had no significant effect on apoptosis. However, the frequency of hepatocyte apoptosis was significantly reduced in HepG2 cells pretreated with M2 medium. Similarly, hepatocyte apoptosis was significantly reduced in HL-7702 cells pretreated with M2 medium. Thus, M2-like macrophages confer strong apoptosis resistance to human hepatocytes .
Wound angiogenesis is an integral part of tissue repair. In wounds by stimulating neovascular sprouting in real time and in vivo, studies of mouse and zebra fish wounds indicate that macrophages are attracted to wound vessels shortly after injury and are closely related to the entire repair process. In addition, macrophage ablation leads to impaired neovascularization. Macrophages not only play a role in the stage of wound repair, but also play a non-negligible role in vascular degeneration. Their activation or loss of activation may impair proper vascular clearance .
Since macrophages play a key role in the pathophysiological process triggered by myocardial infarction (MI), monocytes/ macrophages represent potential therapeutic targets for promoting myocardial repair and functional regeneration . Sestrins is a family of stress-inducing proteins that regulate metabolic homeostasis . In this family of proteins, Sestrin2 is important for protecting myocardium from ischemic injury, and it acts as an LKB1-AMPK scaffold to initiate AMPK signaling after ischemia . The study found that Sestrin2 regulated the role of cardiac macrophage inflammatory response after MI. Cardiac macrophages up-regulated the expression of Sestrin2 in a mouse MI model. Sestrin2 was over-expressed in polarized M1 and M2 macrophages using a lentiviral transduction system, whereas Sestrin2 functions primarily on M1 but not on M2 macrophages. Overexpression of Sestrin2 inhibits the proinflammatory response of M1 macrophages. Furthermore, in the case of a mouse MI model with selective depletion of endogenous macrophages and macrophages over expressing exogenous Sestrin2, antiinflammatory and repair promoting effects of Sestrin2-expressing macrophages were demonstrated .
Macrophages are ubiquitous cells in all major tissues. We know that tissue macrophages in many organs have been colonized and self-renewing during embryonic development, independent of blood mononuclear cells. Under inflammatory conditions, those tissue macrophages are replaced by mononuclear cell-derived macrophages that are linked and sometimes recruited. The function of macrophages in homeostasis and disease depends not only on their developmental origin, but also on the tissue environment. Macrophages have attracted worldwide attention because of their great plasticity and functional diversity. In a disease model, it may be that macrophage M1 first exerts antiinflammatory effects, clears and phagocytose necrotic and apoptotic cells, and then macrophage M2 reconstitutes to promote vascular and tissue production. For macrophages Classification, there is still much controversy in the academic world, but it is clear that the microenvironment and various chemokines in the organization have an indelible contribution to the differentiation of macrophages. Exploring the mechanisms of macrophages in various diseases can sometimes play a crucial role in the disease.
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