Roch Toralf, Akymenko Oksana, Krüger Anne, Jung Friedrich, Ma Nan, Lendlein Andreas
Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Helmholtz-Zentrum Geesthacht, Teltow, Germany Helmholtz Virtual Institute - Multifunctional Biomaterials for Medicine, Teltow and Berlin, Germany.
Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Helmholtz-Zentrum Geesthacht, Teltow, Germany.
Clin Hemorheol Microcirc. 2014;58(1):147-58. doi: 10.3233/CH-141885.
The polarization behavior of macrophages determines the clinical outcome after implantation of biomaterials. Formation of classically activated macrophages (CAM) may result in cell fusion to form foreign body giant cells, which induce and support uncontrolled inflammatory responses and can cause undesired material degradation. In contrast, polarization into alternatively activated macrophages (AAM) is assumed to support healing processes and implant integration. The expression of matrix metalloproteinases (MMP) by the different macrophage subsets might play a crucial role for inflammatory and wound healing processes and may subsequently influence the implant integration. Therefore, it is of importance to characterize the MMP expression pattern by the different macrophage subsets. This knowledge could support the design of biomaterials in which specific MMP cleavage sites are incorporated allowing a controlled cell-mediated degradation of the material. However, it needs to be considered that the pure expression levels may not correlate with the enzymatic activity of the MMP, which depends on a variety of different parameters such as additional co-factors. For this reason, the differential MMP expression levels and the overall enzymatic activity of in vitro generated human non-polarized macrophages (M0), CAM, and AAM are analyzed in this study. While MMP-1, MMP-3, and MMP-10 showed the highest expression levels in CAM, MMP-12 was most strongly expressed by AAM. Interestingly, although various MMP were expressed at high levels in CAM, the enzymatic MMP activity was increased in supernatants of AAM cultures. The data presented here illustrate the importance to combine the measurement of MMP expression levels with the analysis of the enzymatic activity. The observed MMP-12 expression in combination with the higher enzymatic activity detected in AAM supernatants might motivate the design of biomaterials, whose structure could be modified by MMP-12 catalyzed reactions leading to interactive polymers.
巨噬细胞的极化行为决定了生物材料植入后的临床结果。经典活化巨噬细胞（CAM）的形成可能导致细胞融合形成异物巨细胞，从而诱导并支持不受控制的炎症反应，并可能导致不良的材料降解。相比之下，向替代活化巨噬细胞（AAM）的极化被认为有助于愈合过程和植入物整合。不同巨噬细胞亚群中基质金属蛋白酶（MMP）的表达可能在炎症和伤口愈合过程中起关键作用，并可能随后影响植入物整合。因此，表征不同巨噬细胞亚群的MMP表达模式非常重要。这一知识可以支持生物材料的设计，其中包含特定的MMP切割位点，允许对材料进行可控的细胞介导降解。然而，需要考虑的是，纯表达水平可能与MMP的酶活性无关，而酶活性取决于多种不同参数，如其他辅助因子。因此，本研究分析了体外产生的人非极化巨噬细胞（M0）、CAM和AAM的差异MMP表达水平和总体酶活性。虽然MMP-1、MMP-3和MMP-10在CAM中表达水平最高，但MMP-12在AAM中表达最强。有趣的是，尽管CAM中各种MMP的表达水平很高，但AAM培养上清液中的MMP酶活性却有所增加。此处呈现的数据说明了将MMP表达水平的测量与酶活性分析相结合的重要性。在AAM上清液中观察到的MMP-12表达与较高的酶活性相结合，可能会推动生物材料的设计，其结构可以通过MMP-12催化的反应进行修饰，从而形成相互作用的聚合物。
