Biochemistry and Molecular Biology Research Centre for Nanomedicine, Vall Hebron University Hospital, Barcelona, Spain.
Immunobiology. 2012 Jan;217(1):44-53. doi: 10.1016/j.imbio.2011.08.003. Epub 2011 Aug 12.
Several soft-tissue dermal fillers have been reported to provoke immunogenicity and may cause adverse reactions despite claims regarding their safety. This study aimed to assess biomaterial-induced macrophage activation, cell-mediated immune response and oxidative stress in 169 patients with dermal bioimplants. To this end, we analysed plasma concentrations of myeloperoxidase (MPO), the chitinase-like proteins chitotriosidase and YKL-40 and molecular oxidative damage. The present study shows, for the first time, that the components of innate immunity: chitotriosidase and YKL-40, are significantly higher in patients with certain bioimplants and these markers of monocyte/macrophage activation rose progressively as adverse reactions (AR) evolved. Plasma MPO levels increased 4-fold in filler users with AR and 3-fold in those without. Analysis by filler type showed subjects injected with calcium hydroxylapatite, methacrylate, acrylamides and silicone to have values significantly above those of non-filler subjects for at least two plasma biomarkers, probably because the afore-mentioned biomaterials are permanent and prone to trigger AR in the long term. By contrast, hyaluronic acid alone elicited little immune response. Plasma concentrations of markers of oxidative damage to lipids and proteins were found to be significantly higher in users of four of the nine dermal fillers studied. These diffusible products of molecular peroxidation would stem from the reaction catalysed by MPO that generates potent oxidants, leading to cell oxidative damage which, in turn, may exert deleterious effects on the organism. Overall, the results of this study on the effects of a range of dermal fillers point to chronic activation of the immune response mediated by macrophages and PMNs. The increases in plasma of MPO, chitotriosidase and YKL-40 proteins and products of macromolecular peroxidation suggests that these molecules could serve as blood-based biochemical markers and alert to the risk of chronic immune system activation and development of adverse events that may arise from the use of certain bioimplants.
已有报道称，一些软组织真皮填充剂会引起免疫原性，并可能导致不良反应，尽管其安全性已得到相关声明。本研究旨在评估 169 名真皮生物植入物患者的生物材料诱导的巨噬细胞激活、细胞介导的免疫反应和氧化应激。为此，我们分析了髓过氧化物酶 (MPO)、几丁质酶样蛋白壳三糖酶和 YKL-40 以及分子氧化损伤的血浆浓度。本研究首次表明，固有免疫的组成部分：壳三糖酶和 YKL-40，在某些生物植入物患者中明显升高，这些单核细胞/巨噬细胞激活标志物随着不良反应 (AR) 的发展而逐渐升高。AR 患者填充物使用者的血浆 MPO 水平增加了 4 倍，无 AR 患者增加了 3 倍。通过填充物类型分析表明，注射羟基磷灰石钙、甲基丙烯酸盐、丙烯酰胺和硅胶的受试者至少有两种血浆生物标志物的数值明显高于非填充物受试者，这可能是因为上述生物材料是永久性的，容易在长期内引发 AR。相比之下，单独使用透明质酸引起的免疫反应很小。研究的九种真皮填充物中有四种的使用者的脂质和蛋白质的氧化损伤标志物的血浆浓度明显升高。这些可扩散的分子过氧化物产物可能源自 MPO 催化的反应，该反应产生强氧化剂，导致细胞氧化损伤，进而可能对机体造成有害影响。总的来说，本研究对一系列真皮填充物的影响的结果表明，巨噬细胞和 PMN 介导的免疫反应呈慢性激活状态。MPO、壳三糖酶和 YKL-40 蛋白以及大分子过氧化物产物的血浆增加表明，这些分子可以作为基于血液的生化标志物，并提示某些生物植入物的使用可能导致慢性免疫系统激活和不良事件的发生风险。
