Opposing effects of in vitro differentiated macrophages sub-type on epithelial wound healing.
Opposing effects of in vitro differentiated macrophages sub-type on epithelial wound healing.
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DOI：
10.1371/journal.pone.0184386
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Lamb DJ
中科院分区：
文献类型：
--
作者：
Gindele JA;Mang S;Pairet N;Christ I;Gantner F;Schymeinsky J;Lamb DJ
在包括慢性阻塞性肺疾病和特发性肺纤维化在内的许多呼吸系统疾病中，对肺上皮损伤的不适当修复反应与上皮屏障功能紊乱和气道重塑有关。我们建立了体外气液界面机械划痕损伤模型，该模型概括了在人体组织和小动物模型中观察到的上皮损伤过程中观察到的许多特征。创面闭合最初与分化的尖端细胞去分化和快速迁移到创口部位有关，随后伤口边缘后面的尖端细胞增殖，FAK表达增加，纤维连接蛋白和PAI-1减少，共同促进细胞运动和细胞外基质沉积。巨噬细胞与创伤修复密切相关，因此我们试图在一种新的原代人类共培养模型中研究巨噬细胞亚型在这一过程中的作用。M_1巨噬细胞促进FAK表达，M_1和M_2巨噬细胞均促进上皮去分化。有趣的是，M2a巨噬细胞抑制增殖和纤维连接蛋白表达，可能是通过维甲酸途径，而M2b和M2c巨噬细胞抑制纤维连接蛋白沉积，可能是通过基质金属蛋白酶表达。总的来说，这些数据突出了上皮伤口闭合的复杂性，巨噬细胞亚型对这一过程的不同影响，以及这些巨噬细胞的异质性和非描述性功能。
Inappropriate repair responses to pulmonary epithelial injury have been linked to perturbation of epithelial barrier function and airway remodelling in a number of respiratory diseases, including chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. We developed an in vitro mechanical scratch injury model in air-liquid interface differentiated primary human small airway epithelial cells that recapitulates many of the characteristics observed during epithelial wound injury in both human tissue and small animal models. Wound closure was initially associated with de-differentiation of the differentiated apical cells and rapid migration into the wound site, followed by proliferation of apical cells behind the wound edge, together with increases in FAK expression, fibronectin and reduction in PAI-1 which collectively facilitate cell motility and extracellular matrix deposition. Macrophages are intimately involved in wound repair so we sought to investigate the role of macrophage sub-types on this process in a novel primary human co-culture model. M1 macrophages promoted FAK expression and both M1 and M2 macrophages promoted epithelial de-differentiation. Interestingly, M2a macrophages inhibited both proliferation and fibronectin expression, possibly via the retinoic acid pathway, whereas M2b and M2c macrophages prevented fibronectin deposition, possibly via MMP expression. Collectively these data highlight the complex nature of epithelial wound closure, the differential impact of macrophage sub-types on this process, and the heterogenic and non-delineated function of these macrophages.
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影响因子：
3.6
作者：
ERJEFALT, JS;ERJEFALT, I;PERSSON, CGA
通讯作者：
PERSSON, CGA
影响因子：
10
作者：
Erjefalt, JS;Persson, CGA
通讯作者：
Persson, CGA
影响因子：
4
作者：
Schaller, Michael D.
通讯作者：
Schaller, Michael D.
影响因子：
5.7
作者：
Flevaris, Panagiotis;Vaughan, Douglas
通讯作者：
Vaughan, Douglas
DOI：
10.1177/1534734607301394
发表时间：
2007-06-01
期刊：
The international journal of lower extremity wounds
影响因子：
--
作者：
Agren, Magnus S;Werthen, Maria
通讯作者：
Werthen, Maria