Macrophage Polarization in Inflammatory Diseases

Liu, Yan-Cun; Zou, Xian-Biao; Chai, Yan-Fen; Yao, Yong-Ming

TAM polarization is also affected by the spatial location in tumor environment. For example, TAM in hypoxic zones of solid tumors may express Arg1, a marker of M2 phenotype, but this phenomenon is not found in areas near functional vasculature [77] . The high expression of Arg1 in hypoxic zones is related to hypoxia-inducible factor (HIF)-1 and HIF-2, which regulate the suppressive capabilities of TAM and contribute to the TAM recruitment in models of inflammatory hepatocellular and colon carcinoma [78, 79] . Similarly, cytokines secreted by tumor-infiltrating leukocytes in the microenvironment play a pivotal role in the polarization of TAM. For instance, IL-4/IL-13 secreted by tumor-infiltrating Th2 CD4 + T cells contributes to the formation of M2 phenotype. In addition, the intracellular molecules, such as high mobility group box 1 protein (HMGB1), can migrate to the outer space of TAM, bind to the TLRs, and promote the transformation of a pro-inflammatory phenotype in the development of tumors [80] .