Macrophage activation and polarization

Macrophage activation and polarization

January 1, 2008 | Fernando Oneissi Martinez, Antonio Sica, Alberto Mantovani, Massimo Locati
Macrophages play a crucial role in both innate and adaptive immunity, acting as key cells in homeostasis and defense. They can be phenotypically polarized by the microenvironment, leading to specific functional programs. Polarized macrophages are broadly classified into two main groups: classically activated macrophages (M1) and alternatively activated macrophages (M2). M1 macrophages, activated by IFN-gamma and LPS, exhibit strong microbicidal properties and promote Th1 responses. M2 macrophages, further subdivided into M2a, M2b, and M2c, support Th2-associated effector functions and play roles in inflammation resolution through high endocytic clearance and trophic factor synthesis. Tumor-associated macrophages (TAMs) display an alternative-like activation phenotype and have a pro-tumoral role. The polarization paradigm, which mimics the Th1-Th2 paradigm, explains the diverse roles of macrophages in both inflammatory and resolution phases. Understanding the pathogenetic roles of polarized macrophages may lead to novel therapeutic approaches, particularly in cancer. However, many questions remain, and species-specific differences in macrophage polarization need further investigation.Macrophages play a crucial role in both innate and adaptive immunity, acting as key cells in homeostasis and defense. They can be phenotypically polarized by the microenvironment, leading to specific functional programs. Polarized macrophages are broadly classified into two main groups: classically activated macrophages (M1) and alternatively activated macrophages (M2). M1 macrophages, activated by IFN-gamma and LPS, exhibit strong microbicidal properties and promote Th1 responses. M2 macrophages, further subdivided into M2a, M2b, and M2c, support Th2-associated effector functions and play roles in inflammation resolution through high endocytic clearance and trophic factor synthesis. Tumor-associated macrophages (TAMs) display an alternative-like activation phenotype and have a pro-tumoral role. The polarization paradigm, which mimics the Th1-Th2 paradigm, explains the diverse roles of macrophages in both inflammatory and resolution phases. Understanding the pathogenetic roles of polarized macrophages may lead to novel therapeutic approaches, particularly in cancer. However, many questions remain, and species-specific differences in macrophage polarization need further investigation.
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