Trøstrup Hannah, Lerche Christian Johann, Christophersen Lars, Jensen Peter Østrup, Høiby Niels, Moser Claus
Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen, Denmark.
Institute for Immunology and Microbiology, University of Copenhagen, 2100 Copenhagen, Denmark.
Int J Mol Sci. 2017 Jun 26;18(7):1359. doi: 10.3390/ijms18071359.
biofilm maintains and perturbs local host defense, hindering timely wound healing. Previously, we showed that suppressed S100A8/A9 of the murine innate host defense. We assessed the potential antimicrobial effect of S100A8/A9 on biofilm-infected wounds in a murine model and growth in vitro. Seventy-six mice, inflicted with a full-thickness burn wound were challenged subcutaneously (s.c.) by 10⁶ colony-forming units (CFUs) of biofilm. Mice were subsequently randomized into two treatment groups, one group receiving recombinant murine S100A8/A9 and a group of vehicle controls (phosphate-buffered saline, PBS) all treated with s.c. injections daily for up to five days. Wounds were analyzed for quantitative bacteriology and contents of key inflammatory markers. Count of blood polymorphonuclear leukocytes was included. S100A8/A9-treatment ameliorated wound infection, as evaluated by quantitative bacteriology ( ≤ 0.05). In vitro, growth of was inhibited dose-dependently by S100A8/A9 in concentrations from 5 to 40 μg/mL, as determined by optical density-measurement (OD-measurement) and quantitative bacteriology. Treatment slightly augmented key inflammatory cytokine Tumor Necrosis Factor-α (TNF-α), but dampened interferon-γ (IFN-γ) levels and blood polymorphonuclear count. In conclusion, topical S100A8/A9 displays remarkable novel immune stimulatory and anti-infective properties in vivo and in vitro. Importantly, treatment by S100A8/A9 provides local infection control. Implications for a role as adjunctive treatment in healing of chronic biofilm-infected wounds are discussed.
生物膜维持并扰乱局部宿主防御，阻碍伤口及时愈合。此前，我们发现小鼠固有宿主防御中的S100A8/A9受到抑制。我们在小鼠模型中评估了S100A8/A9对生物膜感染伤口的潜在抗菌作用以及体外生长情况。76只遭受全层烧伤伤口的小鼠皮下接种10⁶个生物膜菌落形成单位（CFU）。随后将小鼠随机分为两个治疗组，一组接受重组小鼠S100A8/A9，另一组为载体对照组（磷酸盐缓冲盐水，PBS），两组均每天皮下注射，持续五天。对伤口进行定量细菌学分析和关键炎症标志物含量检测。包括血液多形核白细胞计数。通过定量细菌学评估，S100A8/A9治疗改善了伤口感染（P≤0.05）。在体外，通过光密度测量（OD测量）和定量细菌学确定，S100A8/A9在5至40μg/mL的浓度范围内对其生长具有剂量依赖性抑制作用。治疗轻微增加了关键炎症细胞因子肿瘤坏死因子-α（TNF-α），但降低了干扰素-γ（IFN-γ）水平和血液多形核细胞计数。总之，局部应用S100A8/A9在体内和体外均显示出显著的新型免疫刺激和抗感染特性。重要的是，S100A8/A9治疗可实现局部感染控制。讨论了其作为慢性生物膜感染伤口愈合辅助治疗的作用。
