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Abstract
Inflammation is a normal physiological response to an infection or injury, such as aggression by microbes, trauma, or heat and radiation. Inflammation works to maintain homeostasis and is a highly regulated process with both pro- and anti-inflammatory components to ensure the prompt resolution of noxious conditions. In the initial stages of inflammation, macrophages destroy the abnormal stimuli, and remove the apoptotic bodies of the dead neutrophils as well as any remaining hazard factor. The macrophages then present the antigen to T lymphocytes to initiate the mechanisms of acquired immunity, which leads to the production of antibodies, cytokines and memory cells. The macrophage activity then switches from proinflammatory to antiinflammatory to remove any elements of aggression, thereby achieving homeostasis. Macrophages play a key role in the innate immune response and form a bridge between the innate and acquired immune response. In certain circumstances, however, when chronic inflammation is produced, macrophages may have a harmful effect and cause lesions. Therefore, inflammation is the classic “double-edged sword”, in which macrophages cut both ways. Activated macrophages have two different phenotypes related to different stimuli: M1 (classically activated) and M2 (alternatively activated). M1 macrophages are proinflammatory and play a key role in the host defense mechanism, while M2 are associated with the responses to anti-inflammatory reactions and tissue remodeling. The transformation of different phenotypes of macrophages regulates the initiation, development, and cessation of inflammatory diseases. An imbalance of macrophage M1∼ M2 polarization is often associated with a range of diseases or inflammatory conditions, such as rheumatoid arthritis and systemic lupus erythematous. (J Rheum Dis 2018;25:11-18)
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Figure 1.
M1 and M2 macrophage polarizing pathways. TLR: toll-like receptor, NLR: nod-like receptor, IFN: interferon, CSF2R: colony stimulating factor 2 receptor, IRF: interferon regulatory factor, NF: nuclear factor, HIF: hypoxia-inducible factors, STAT: signal transducer and activator of transcription, SOCS: suppressor of cytokine signaling, miR: microRNA, GM-CSF: granulocyte macrophage colony-stimulating factor, LPS: lipopolysaccharide, PAMP: pathogen-associated molecular patterns, IL: interleukin, PPAR γ: peroxisome proliferator activated receptor γ, C-Maf: cellular muscular aponeurotic fibrosarcoma.
Figure 2.
Macrophage and apoptosis. Apoptotic cells are recognized by their lipid phospha-tidylserine (blue) on the plasma membrane and, subsequently, are removed by phagocytosis. In addition, apoptotic cells produce other signals (colored rectangles) that control the outcome of their recognition by macrophages, but its consequences are likely to rely on the cause of cell death.
Table 1.
Subset of macrophage polarization
PAMPs: pathogen-associated molecular patterns, DAMPs: danger-associated molecular patterns, IFN: interferon, GM-CSF: granulocyte macrophage colony-stimulating factor, TNF: tumor necrosis factor, IL: interleukin, Arg-1: arginase-1, Chi313: chitinase3-like protein 3, TLR: toll-like receptor, TGF-β: transforming growth factor-β, VEGF: vascular endothelial growth factor.
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