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The response of macrophages to titanium particles is determined by macrophage polarization

机译:巨噬细胞对钛颗粒的反应由巨噬细胞极化决定

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Aseptic loosening of total joint replacements is driven by the reaction of macrophages to foreign body particles released from the implant. It was hypothesized that the macrophages' response to these particles is dependent, in addition to particle characteristics and contaminating biomolecules, on the state of macrophage polarization as determined by the local cytokine microenvironment. To test this hypothesis we differentiated M1 and M2 macrophages from human peripheral blood monocytes and compared their responses to titanium particles using genome-wide microarray analysis and a multiplex cytokine assay. In comparison to non-activated M0 macrophages, the overall chemotactic and inflammatory responses to titanium particles were greatly enhanced in M1 macrophages and effectively suppressed in M2 macrophages. In addition, the genome-wide approach revealed several novel, potentially osteolytic, particle-induced mediators, and signaling pathway analysis suggested the involvement of toll-like and nod-like receptor signaling in particle recognition. It is concluded that the magnitude of foreign body reaction caused by titanium particles is dependent on the state of macrophage polarization. Thus, by limiting the action of M1 polarizing factors, e.g. bacterial biofilm formation, in peri-implant tissues and promoting M2 macrophage polarization by biomaterial solutions or pharmacologically, it might be possible to restrict wear-particle-induced inflammation and osteolysis.
机译:巨噬细胞对植入物释放的异物颗粒的反应驱动了整个关节置换的无菌性松动。假设巨噬细胞对这些颗粒的反应,除了颗粒特征和污染生物分子之外,还取决于由局部细胞因子微环境确定的巨噬细胞极化状态。为了检验这一假设,我们从人类外周血单核细胞中区分了M1和M2巨噬细胞,并使用全基因组微阵列分析和多重细胞因子分析比较了它们对钛颗粒的反应。与未活化的M0巨噬细胞相比,M1巨噬细胞对钛粒子的总体趋化和炎症反应大大增强,而M2巨噬细胞则得到有效抑制。此外,全基因组方法揭示了几种新型的,可能是溶骨性的,颗粒诱导的介体,并且信号通路分析表明,toll​​样和nod样受体信号参与了颗粒识别。结论是钛颗粒引起的异物反应的大小取决于巨噬细胞极化状态。因此,通过限制M1偏振因子的作用,例如在植入物周围组织中形成细菌生物膜并通过生物材料溶液或药理作用促进M2巨噬细胞极化,有可能限制磨损颗粒引起的炎症和骨溶解。

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