Loss of monocyte chemoattractant protein-1 alters macrophage polarization and reduces NFκB activation in the foreign body response.
Loss of monocyte chemoattractant protein-1 alters macrophage polarization and reduces NFκB activation in the foreign body response.
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DOI：
10.1016/j.actbio.2014.09.022
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发表时间：
2015-01
影响因子：
9.7
通讯作者：
Kyriakides, Themis R.
中科院分区：
文献类型：
--
作者：
Moore, Laura Beth;Sawyer, Andrew J.;Charokopos, Antonios;Skokos, Eleni A.;Kyriakides, Themis R.
生物材料植入引起异物反应，其特征是巨噬细胞融合形成异物巨细胞和纤维性包膜。对这种反应中巨噬细胞极化的研究表明，交替激活(M2)与更有利的结果相关。在这里，我们通过在WT和MCP-1KO小鼠的腹膜内植入混合纤维素酯过滤器或PDMS圆盘来研究这一过程。我们通过Q-PCR、免疫组织化学和ELISA法分析了通过灌洗分离的非贴壁细胞和种植贴壁细胞中经典(M1)和替代(M2)基因的表达。我们的结果表明，巨噬细胞经历了独特的激活，表现出M1和M2极化的特征，包括诱导肿瘤坏死因子，诱导免疫荧光和免疫印迹确定的p50和relA的表达和核转位。在体外和体内，融合缺陷的MCP-1 KO巨噬细胞的这两个过程都受到了损害。此外，包括BAY11-7028，一种核因子κB激活的抑制剂，减少了WT巨噬细胞RELA的核转位和融合。我们的研究表明，腹膜植入物诱导了一种独特的巨噬细胞极化表型，导致肿瘤坏死因子的诱导和核因子κB途径的激活。
Implantation of biomaterials elicits a foreign body response characterized by fusion of macrophages to form foreign body giant cells and fibrotic encapsulation. Studies of macrophage polarization in this response have suggested that alternative (M2) activation is associated with more favorable outcomes. Here we investigated this process in vivo by implanting mixed cellulose ester filters or PDMS disks in the peritoneal cavity of WT and MCP-1 KO mice. We analyzed classical (M1) and alternative (M2) gene expression via Q-PCR, immunohistochemistry, and ELISA in both non-adherent cells isolated by lavage and implant-adherent cells. Our results show that macrophages undergo unique activation that displays features of both M1 and M2 polarization including induction of TNF, which induces the expression and nuclear translocation of p50 and RelA determined by immunofluorescence and western blot. Both processes were compromised in fusion-deficient MCP-1 KO macrophages in vitro and in vivo. Furthermore, inclusion of BAY 11-7028, an inhibitor of NFκB activation, reduced nuclear translocation of RelA and fusion in WT macrophages. Our studies suggest that peritoneal implants elicit a unique macrophage polarization phenotype leading to induction of TNF and activation of the NFκB pathway.
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影响因子：
14
作者：
Holt, Dolly J.;Chamberlain, Lisa M.;Grainger, David W.
通讯作者：
Grainger, David W.
影响因子：
6
作者：
Fang, Yujiang;Wei, Yongzhong;Braley-Mullen, Helen
通讯作者：
Braley-Mullen, Helen
影响因子：
3.7
作者：
Di Giuseppe M;Gambelli F;Hoyle GW;Lungarella G;Studer SM;Richards T;Yousem S;McCurry K;Dauber J;Kaminski N;Leikauf G;Ortiz LA
通讯作者：
Ortiz LA
影响因子：
4.8
作者：
Kassiri, Zamaneh;Defamie, Virginie;Khokha, Rama
通讯作者：
Khokha, Rama
DOI：
10.1073/pnas.1006442107
发表时间：
2010-08-24
影响因子：
11.1
作者：
Madden, Lauran R.;Mortisen, Derek J.;Ratner, Buddy D.
通讯作者：
Ratner, Buddy D.