Macrophages

Macrophage is a type of phagocyte that engulfs and digests pathogens and apoptotic cells. Macrophages are produced by the differentiation of monocytes, which turn into macrophages when they leave the blood. These macrophages are found in virtually all tissues where they patrol for potential pathogens by amoeboid movement. They have various forms throughout the body, such as histiocytes, Kupffer cells, alveolar macrophages, microglia, etc., but all are part of the mononuclear phagocyte system. In addition to phagocytosis, they play a key role in non-specific defense (innate immunity) and also help to initiate specific defense mechanisms (adaptive immunity) by recruiting other immune cells.

Macrophages are extremely plastic cells that can rapidly change their functional profile through a process called polarization. Macrophage polarization is indeed the process by which macrophages respond to stimuli from the local microenvironment and acquire a specific functional phenotype. According to their polarization status, macrophages can be divided into M0, M1 (classically activated or pro-inflammatory), and M2 (alternatively activated or anti-inflammatory) macrophages.

M0 macrophages can be considered as naive macrophages that have not been exposed to any pro- or anti-inflammatory stimulus or environment.

M1 macrophages are activated, typically by IFN-γ or lipopolysaccharide (LPS), and produce pro-inflammatory cytokines, phagocytize microbes, and trigger an immune response. M1 macrophages produce nitric oxide (NO) or reactive oxygen intermediates (ROI) to protect against bacteria and viruses.

M2 macrophages are activated by exposure to certain cytokines such as IL-4, IL-10, or IL-13. M2 macrophages will produce either polyamines to induce proliferation or proline to induce collagen production. These macrophages are involved in wound healing and tissue repair. M2 macrophages can be further divided into M2a, M2b, M2c, and M2d depending on their stimulus for the activation. The M2 macrophages induced by IL-4 or IL-13 are called M2a, M2b macrophages are induced by poly IC or TLR or IL-1R agonists, and M2c are induced by IL-10 and glucocorticoids. M2d macrophages, also known as tumor-associated macrophages (TAMs), are induced by TLR ligands and A2 adenosine receptor (A2R) agonists, or by IL-6, and contribute to tumor angiogenesis, growth and metastasis.