Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Cell Metab. 2014 Jan 7;19(1):162-171. doi: 10.1016/j.cmet.2013.11.017. Epub 2013 Dec 26.
Adipose tissue (AT) of obese mice and humans accumulates immune cells, which secrete cytokines that can promote insulin resistance. AT macrophages (ATMs) are thought to originate from bone-marrow-derived monocytes, which infiltrate the tissue from the circulation. Here, we show that a major fraction of macrophages unexpectedly undergo cell division locally within AT, as detected by Ki67 expression and 5-ethynyl-2'-deoxyuridine incorporation. Macrophages within the visceral AT (VAT), but not those in other tissues (including liver and spleen), displayed increased proliferation in obesity. Importantly, depletion of blood monocytes had no impact on ATM content, whereas their proliferation in situ continued. Treatment with monocyte chemotactic protein 1 (MCP-1) induced macrophage cell division in AT explants, whereas mcp-1 deficiency in vivo decreased ATM proliferation. These results reveal that, in addition to blood monocyte recruitment, in situ proliferation driven by MCP-1 is an important process by which macrophages accumulate in the VAT in obesity.
肥胖小鼠和人类的脂肪组织 (AT) 会积累免疫细胞，这些细胞分泌的细胞因子可促进胰岛素抵抗。人们认为 AT 中的巨噬细胞 (ATMs) 来源于骨髓衍生的单核细胞，这些单核细胞从循环系统中渗透到组织中。在这里，我们发现，很大一部分巨噬细胞出乎意料地在 AT 内局部进行细胞分裂，这可通过 Ki67 表达和 5-乙炔基-2'-脱氧尿苷掺入来检测。内脏脂肪组织 (VAT) 中的巨噬细胞，但不是其他组织 (包括肝脏和脾脏) 中的巨噬细胞，在肥胖中表现出增殖增加。重要的是，清除血液单核细胞对 ATM 含量没有影响，而它们的原位增殖仍在继续。单核细胞趋化蛋白 1 (MCP-1) 的处理诱导了 AT 外植体中的巨噬细胞细胞分裂，而体内的 mcp-1 缺乏则降低了 ATM 增殖。这些结果表明，除了血液单核细胞募集外，由 MCP-1 驱动的原位增殖是巨噬细胞在肥胖的 VAT 中积累的一个重要过程。
