Aging Affects Bone Marrow Macrophage Polarization: Relevance to Bone Healing

作者：E. Gibon, F. Loi, L. Córdova, J. Pajarinen, T. Lin, L. Lu, A. Nabeshima, Z. Yao, S. Goodman · 发表于：Regenerative Engineering and Translational Medicine · 年份：2016 · DOI：10.1007/s40883-016-0016-5 · 被引用次数：84 · 研究领域：Medicine

Macrophages are an important component of the inflammatory cascade by initiating and modulating the processes leading to tissue regeneration and bone healing. Depending on the local environment, macrophages can be polarized into M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotypes. In order to assess the effects of aging on macrophage function, bone marrow macrophage polarization using primary bone marrow macrophages (BMMs) from young (8 weeks old) and aged (72 weeks old) wild-type male C57BL/6J mice was analyzed. Fluorescence-activated cell sorting (FACS) analysis (CD11b, iNOS, CD206), qRT-PCR (iNOS, TNF-α, CD206, Arginase 1), and ELISA (TNF-α, IL-1ra) were performed to compare the M1 and M2 phenotypic markers in young and aged mouse macrophages. Once M1 and M2 macrophage phenotypes were confirmed, the results showed that TNF-α mRNA was significantly upregulated in aged M1s after interferon gamma (INF-γ) exposure. Arginase 1 and CD206 mRNA expression were still upregulated with IL4 stimulation in aged macrophages, but to a lesser extend than those from younger animals. TNF-α secretion was also significantly increased in aged M1s compared to young M1s, following lipopolysaccharide (LPS) exposure. However, the IL-1ra secretion did not increase accordingly in aged mice. The results demonstrate that, compared to younger animals, aging of bone marrow derived macrophages increases the resting levels of oxidative stress, and the ratios of pro- to anti-inflammatory markers. Th...