Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany.
Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany
Br J Anaesth. 2015 Mar;114(3):509-19. doi: 10.1093/bja/aeu340. Epub 2014 Oct 16.
During systemic inflammation, leucocytes are activated and extravasate into damaged tissue. Activation and recruitment are influenced by different mechanisms, including the interaction of leucocytes with platelets and neutrophil extracellular traps (NET) formation. Here, we investigated the molecular mechanism by which hydroxyethyl starch (HES 130/0.4) dampens systemic inflammation in vivo.
Systemic inflammation was induced in C57Bl/6 wild-type mice by caecal ligation and puncture and cytokine concentrations in the blood, neutrophil recruitment, platelet-neutrophil aggregates, and NET formation were investigated in vivo. Intravascular adherent and transmigrated neutrophils were analysed by intravital microscopy (IVM) of the cremaster muscle and the kidneys. Flow chamber assays were used to investigate the different steps of the leucocyte recruitment cascade.
By using flow cytometry, we demonstrated that HES 130/0.4 reduces neutrophil recruitment into the lung, liver, and kidneys during systemic inflammation (n=8 mice per group). IVM revealed a reduced number of adherent and transmigrated neutrophils in the cremaster and kidney after HES 130/0.4 administration (n=8 mice per group). Flow chamber experiments showed that HES 130/0.4 significantly reduced chemokine-induced neutrophil arrest (n=4 mice per group). Furthermore, HES 130/0.4 significantly reduced the formation of platelet-neutrophil aggregates, and NET formation during systemic inflammation (n=8 mice per group).
Our findings suggest that HES 130/0.4 significantly reduces neutrophil-platelet aggregates, NET formation, chemokine-induced arrest, and transmigration of neutrophils under inflammatory conditions.
在全身炎症反应中，白细胞被激活并渗出到受损组织中。白细胞的激活和募集受多种机制影响，包括白细胞与血小板的相互作用和中性粒细胞胞外诱捕网（NET）的形成。在这里，我们研究了羟乙基淀粉（HES 130/0.4）在体内抑制全身炎症反应的分子机制。
通过盲肠结扎和穿孔术诱导 C57Bl/6 野生型小鼠全身炎症，并在体内研究血液中的细胞因子浓度、中性粒细胞募集、血小板-中性粒细胞聚集和 NET 形成。通过肧丸肌和肾脏的活体显微镜检查（IVM）分析血管内黏附和迁移的中性粒细胞。使用流动室实验研究白细胞募集级联的不同步骤。
通过流式细胞术，我们证明 HES 130/0.4 可减少全身炎症时肺、肝和肾中的中性粒细胞募集（每组 8 只小鼠）。IVM 显示 HES 130/0.4 给药后肧丸肌和肾脏中黏附和迁移的中性粒细胞数量减少（每组 8 只小鼠）。流动室实验表明，HES 130/0.4 可显著减少趋化因子诱导的中性粒细胞阻滞（每组 4 只小鼠）。此外，HES 130/0.4 可显著减少全身炎症时血小板-中性粒细胞聚集和 NET 形成（每组 8 只小鼠）。
我们的研究结果表明，HES 130/0.4 可显著减少中性粒细胞-血小板聚集物、NET 形成、趋化因子诱导的阻滞和炎症条件下中性粒细胞的迁移。
