Characterization of distinct subpopulations of hepatic macrophages in HFD/obese mice.
Characterization of distinct subpopulations of hepatic macrophages in HFD/obese mice.
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作者：
Morinaga H;Mayoral R;Heinrichsdorff J;Osborn O;Franck N;Hah N;Walenta E;Bandyopadhyay G;Pessentheiner AR;Chi TJ;Chung H;Bogner-Strauss JG;Evans RM;Olefsky JM;Oh DY
目前的教条是，肥胖相关的肝脏炎症是由于库普弗细胞 (KC) 激活增加所致。然而，最近研究表明，在肥胖背景下，招募的肝巨噬细胞（RHM）代表了相当大的肝巨噬细胞群体。因此，我们评估了 KC 和 RHM 或两者是否代表肥胖中的主要肝脏炎症细胞类型。我们结合使用了体内巨噬细胞追踪方法和过继转移技术，其中 KC 和 RHM 用荧光标记进行差异标记。通过这些方法，在瘦和肥胖条件下确定了这些不同巨噬细胞群的炎症表型。体内巨噬细胞追踪显示，肥胖小鼠的 RHM 数量大约是瘦小鼠的六倍，而 KC 的数量相当。此外，与 KC 相比，RHM 包含较小的尺寸和不成熟的单核细胞来源的细胞。此外，与瘦小鼠的 RHM 相比，肥胖小鼠的 RHM 发炎程度更高，肿瘤坏死因子-α 和白细胞介素 6 表达水平更高。两种细胞类型之间的 MCP-1/C-C 趋化因子受体 2 型 (CCR2) 趋化因子系统的比较表明，配体 (MCP-1) 在 KC 中比在 RHM 中表达更高，而 CCR2 表达在 RHM 中大约高五倍。我们得出的结论是，KC 可以通过引起 RHM 的募集来参与肥胖引起的炎症，而 RHM 与 KC 不同，并且不是 KC 的前体。这些 RHM 会增强肥胖引起的炎症和肝脏胰岛素抵抗的严重程度。
The current dogma is that obesity-associated hepatic inflammation is due to increased Kupffer cell (KC) activation. However, recruited hepatic macrophages (RHMs) were recently shown to represent a sizable liver macrophage population in the context of obesity. Therefore, we assessed whether KCs and RHMs, or both, represent the major liver inflammatory cell type in obesity. We used a combination of in vivo macrophage tracking methodologies and adoptive transfer techniques in which KCs and RHMs are differentially labeled with fluorescent markers. With these approaches, the inflammatory phenotype of these distinct macrophage populations was determined under lean and obese conditions. In vivo macrophage tracking revealed an approximately sixfold higher number of RHMs in obese mice than in lean mice, whereas the number of KCs was comparable. In addition, RHMs comprised smaller size and immature, monocyte-derived cells compared with KCs. Furthermore, RHMs from obese mice were more inflamed and expressed higher levels of tumor necrosis factor-α and interleukin-6 than RHMs from lean mice. A comparison of the MCP-1/C-C chemokine receptor type 2 (CCR2) chemokine system between the two cell types showed that the ligand (MCP-1) is more highly expressed in KCs than in RHMs, whereas CCR2 expression is approximately fivefold greater in RHMs. We conclude that KCs can participate in obesity-induced inflammation by causing the recruitment of RHMs, which are distinct from KCs and are not precursors to KCs. These RHMs then enhance the severity of obesity-induced inflammation and hepatic insulin resistance.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
7.7
作者：
Marchesini, G;Brizi, M;Melchionda, N
通讯作者：
Melchionda, N
影响因子：
16.6
作者：
Jia, Lin;Vianna, Claudia R.;Fukuda, Makoto;Berglund, Eric D.;Liu, Chen;Tao, Caroline;Sun, Kai;Liu, Tiemin;Harper, Matthew J.;Lee, Charlotte E.;Lee, Syann;Scherer, Philipp E.;Elmquist, Joel K.
通讯作者：
Elmquist, Joel K.
影响因子：
13.5
作者：
Mandrekar, Pranoti;Ambade, Aditya;Lim, Arlene;Szabo, Gyongyi;Catalano, Donna
通讯作者：
Catalano, Donna
DOI：
10.1016/j.bbadis.2009.08.007
发表时间：
2009-11
影响因子：
6.2
作者：
Clementi, Alicia H.;Gaudy, Allison M.;van Rooijen, Nico;Pierce, Robert H.;Mooney, Robert A.
通讯作者：
Mooney, Robert A.