Artificial extracellular matrices composed of collagen I and high-sulfated hyaluronan promote phenotypic and functional modulation of human pro-inflammatory M1 macrophages
Artificial extracellular matrices composed of collagen I and high-sulfated hyaluronan promote phenotypic and functional modulation of human pro-inflammatory M1 macrophages
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DOI：
10.1016/j.actbio.2012.11.016
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发表时间：
2013-03-01
影响因子：
9.7
通讯作者：
Simon, Jan C.
中科院分区：
文献类型：
--
作者：
Franz, Sandra;Allenstein, Francie;Simon, Jan C.
生物材料整合和伤口愈合的连续阶段需要由不同的巨噬细胞亚群介导的不同的巨噬细胞功能。在愈合的初始阶段，需要促炎性M1巨噬细胞（M Phi 1）来清除伤口中的微生物和碎片;然而，它们的无抵抗的持续激活通常会导致生物材料的整合受到干扰，伤口愈合受到干扰。在这里，我们研究了促炎巨噬细胞功能是否受到基于人工细胞外基质（aECM）的免疫调节生物材料的影响。为了解决这个问题，我们测试了由胶原蛋白I和透明质酸或透明质酸的硫酸化衍生物组成的二维aECM影响体外极化的人促炎性M Phi 1的功能的能力。含有高硫酸化透明质酸的aECM显著降低了炎性巨噬细胞功能，包括病原体摄取和促炎性细胞因子肿瘤坏死因子α和白细胞介素-12的释放，这是由于活化的B细胞的核因子“κ-轻链增强子”的活化受损。此外，这些巨噬细胞分泌免疫调节IL-10，并显示转录因子信号转导子和转录激活子1和干扰素调节因子5的活性降低，两者都控制巨噬细胞极化至M Phi 1亚群。我们的数据显示，含有高硫酸化透明质酸的胶原蛋白I基质具有免疫调节特性，并通过阻碍对促炎性M Phi 1极化至关重要的信号传导途径来抑制炎性巨噬细胞活性。因此，我们建议将这种aECM作为生物材料的有希望的涂层，以在愈合反应期间调节炎性巨噬细胞功能，并建议将其作为三种治疗方法进行进一步测试。三维构建体和体内模型。(c)2012 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
The sequential phases of biomaterial integration and wound healing require different macrophage functions mediated by distinct macrophage subsets. During the initial phase of healing, pro-inflammatory M1 macrophages (M Phi 1) are required to clear the wound from microbes and debris; however, their unopposed, persistent activation often leads to disturbed integration of biomaterials and perturbed wound healing. Here we investigated whether pro-inflammatory macrophage functions are affected by immunomodulatory biomaterials based on artificial extracellular matrices (aECM). To address this issue, we tested the capacity of two-dimensional aECM consisting of collagen I and hyaluronan or sulfated derivatives of hyaluronan to affect functions of in vitro polarized human pro-inflammatory M Phi 1. The aECM containing high-sulfated hyaluronan substantially decreased inflammatory macrophage functions, including pathogen uptake and release of the pro-inflammatory cytokines tumor necrosis factor alpha and interleukin-12 due to impaired activation of nuclear factor "kappa-light-chain-enhancer" of activated B-cells. Moreover, these macrophages secreted immunregulatory IL-10 and showed reduced activity of the transcription factors signal transducer and activator of transcription 1 and interferon-regulating factor 5, both controlling macrophage polarization to M Phi 1 subsets. Our data reveal that the collagen I matrix containing high-sulfated hyaluronan possesses immunomodulating properties and dampens inflammatory macrophage activities by impeding signaling pathways crucial for polarization of pro-inflammatory M Phi 1 We therefore suggest this aECM as a promising coating for biomaterials to modulate inflammatory macrophage functions during the healing response and recommend its further testing as a three-dimensional construct and in in vivo models. (c) 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.