Department of Medicine, University of California, San Diego, La Jolla, California, USA.
Diabetes. 2012 Feb;61(2):346-54. doi: 10.2337/db11-0860. Epub 2011 Dec 21.
Macrophage-mediated inflammation is a key component of insulin resistance; however, the initial events of monocyte migration to become tissue macrophages remain poorly understood. We report a new method to quantitate in vivo macrophage tracking (i.e., blood monocytes from donor mice) labeled ex vivo with fluorescent PKH26 dye and injected into recipient mice. Labeled monocytes appear as adipose, liver, and splenic macrophages, peaking in 1-2 days. When CCR2 KO monocytes are injected into wild-type (WT) recipients, or WT monocytes given to MCP-1 KO recipients, adipose tissue macrophage (ATM) accumulation is reduced by ~40%, whereas hepatic macrophage content is decreased by ~80%. Using WT donor cells, ATM accumulation is several-fold greater in obese recipient mice compared with lean mice, regardless of the source of donor monocytes. After their appearance in adipose tissue, ATMs progressively polarize from the M2- to the M1-like state in obesity. In summary, the CCR2/MCP-1 system is a contributory factor to monocyte migration into adipose tissue and is the dominant signal controlling the appearance of recruited macrophages in the liver. Monocytes from obese mice are not programmed to become inflammatory ATMs but rather the increased proinflammatory ATM accumulation in obesity is in response to tissue signals.
巨噬细胞介导的炎症是胰岛素抵抗的一个关键组成部分；然而，单核细胞迁移成为组织巨噬细胞的初始事件仍知之甚少。我们报告了一种新的方法来定量体内巨噬细胞追踪（即，来自供体小鼠的血液单核细胞），这些单核细胞在体外用荧光 PKH26 染料标记，并注射到受体小鼠中。标记的单核细胞表现为脂肪、肝脏和脾脏巨噬细胞，在 1-2 天内达到峰值。当 CCR2 KO 单核细胞被注射到野生型（WT）受体中，或 WT 单核细胞被给予 MCP-1 KO 受体时，脂肪组织巨噬细胞（ATM）的积累减少了约 40%，而肝巨噬细胞的含量减少了约 80%。使用 WT 供体细胞，与瘦小鼠相比，肥胖受体小鼠中的 ATM 积累要高出数倍，而不管供体单核细胞的来源如何。在脂肪组织中出现后，ATMs 在肥胖中从 M2 样状态逐渐向 M1 样状态极化。总之，CCR2/MCP-1 系统是单核细胞迁移进入脂肪组织的一个促成因素，是控制肝脏募集巨噬细胞出现的主要信号。肥胖小鼠的单核细胞没有被编程成为炎症性 ATMs，而是肥胖中增加的促炎 ATM 积累是对组织信号的反应。
