Introduction Zinc is well known for its anti-inflammatory effects, including regulation of migration and activity of polymorphonuclear neutrophils (PMN). Zinc deficiency is associated with inflammatory diseases such as acute lung injury (ALI). As deregulated neutrophil recruitment and their hyper-activation are hallmarks of ALI, benefits of zinc supplementation on the development of lipopolysaccharides (LPS)-induced ALI were tested. Methods 64 C57Bl/6 mice, split into eight groups, were injected with 30 µg zinc 24 hours before exposure to aerosolised LPS for 4 hours. Zinc homoeostasis was characterised measuring serum and lung zinc concentrations as well as metallothionein-1 expression. Recruitment of neutrophils to alveolar, interstitial and intravascular space was assessed using flow cytometry. To determine the extent of lung damage, permeability and histological changes and the influx of protein into the bronchoalveolar lavage fluid were measured. Inflammatory status and PMN activity were evaluated via tumour necrosis factor α levels and formation of neutrophil extracellular traps. The effects of zinc supplementation prior to LPS stimulation on activation of primary human granulocytes and integrity of human lung cell monolayers were assessed as well. Results Injecting zinc 24 hours prior to LPS-induced ALI indeed significantly decreased the recruitment of neutrophils to the lungs and prevented their hyperactivity and thus lung damage was decreased. Results from in vitro investigations using human cells suggest the transferability of the finding to human disease, which remains to be tested in more detail. Conclusion Zinc supplementation attenuated LPS-induced lung injury in a murine ALI model. Thus, the usage of zinc-based strategies should be considered to prevent detrimental consequences of respiratory infection and lung damage in risk groups.

中文翻译：

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锌补充剂通过减少中性粒细胞的募集和活动来改善肺损伤

简介 锌以其抗炎作用而闻名，包括调节多形核中性粒细胞 (PMN) 的迁移和活性。缺锌与急性肺损伤 (ALI) 等炎症性疾病有关。由于中性粒细胞募集失调及其过度激活是 ALI 的标志，因此测试了补锌对脂多糖 (LPS) 诱导的 ALI 发展的益处。方法 将 64 只 C57Bl/6 小鼠分成八组，在暴露于雾化 LPS 4 小时前 24 小时注射 30 µg 锌。锌稳态通过测量血清和肺锌浓度以及金属硫蛋白-1 表达来表征。使用流式细胞术评估中性粒细胞向肺泡、间质和血管内空间的募集。为了确定肺损伤的程度，测量渗透性和组织学变化以及蛋白质流入支气管肺泡灌洗液。通过肿瘤坏死因子 α 水平和中性粒细胞胞外陷阱的形成评估炎症状态和 PMN 活性。还评估了在 LPS 刺激之前补充锌对原代人粒细胞活化和人肺细胞单层完整性的影响。结果 在 LPS 诱导的 ALI 之前 24 小时注射锌确实显着减少了向肺部募集中性粒细胞并防止其过度活跃，从而减少了肺损伤。使用人类细胞进行的体外研究结果表明，该发现可应用于人类疾病，这仍有待更详细的测试。结论 补锌可减轻小鼠 ALI 模型中 LPS 诱导的肺损伤。因此，应考虑使用基于锌的策略，以防止风险人群中呼吸道感染和肺损伤的有害后果。