ZIK plasmatis Leibniz Institute for Plasma Science and Technology (INP) Felix-Hausdorff-Str. 2 Greifswald 17489 Germany.
Department of General Visceral Thoracic and Vascular Surgery University Medicine Greifswald Sauerbruchstr. DZ7 Greifswald 17475 Germany.
Adv Sci (Weinh). 2021 Mar 8;8(10):2003395. doi: 10.1002/advs.202003395. eCollection 2021 May.
Reactive oxygen species (ROS/RNS) are produced during inflammation and elicit protein modifications, but the immunological consequences are largely unknown. Gas plasma technology capable of generating an unmatched variety of ROS/RNS is deployed to mimic inflammation and study the significance of ROS/RNS modifications using the model protein chicken ovalbumin (Ova vs oxOva). Dynamic light scattering and circular dichroism spectroscopy reveal structural modifications in oxOva compared to Ova. T cells from Ova-specific OT-II but not from C57BL/6 or SKH-1 wild type mice presents enhanced activation after Ova addition. OxOva exacerbates this activation when administered ex vivo or in vivo, along with an increased interferon-gamma production, a known anti-melanoma agent. OxOva vaccination of wild type mice followed by inoculation of syngeneic B16F10 Ova-expressing melanoma cells shows enhanced T cell number and activation, decreased tumor burden, and elevated numbers of antigen-presenting cells when compared to their Ova-vaccinated counterparts. Analysis of oxOva using mass spectrometry identifies three hot spots regions rich in oxidative modifications that are associated with the increased T cell activation. Using Ova as a model protein, the findings suggest an immunomodulating role of multi-ROS/RNS modifications that may spur novel research lines in inflammation research and for vaccination strategies in oncology.
活性氧（ROS/RNS）在炎症期间产生，并引起蛋白质修饰，但免疫后果在很大程度上尚不清楚。气体等离子体技术能够产生无与伦比的多种 ROS/RNS，可用于模拟炎症，并使用模型蛋白鸡卵清蛋白（Ova 与 oxOva）研究 ROS/RNS 修饰的意义。动态光散射和圆二色性光谱显示 oxOva 与 Ova 相比结构发生了修饰。来自 Ova 特异性 OT-II 的 T 细胞，但不是来自 C57BL/6 或 SKH-1 野生型小鼠的 T 细胞，在添加 Ova 后表现出增强的激活。oxOva 在外源或体内给药时会加剧这种激活，同时增加干扰素-γ的产生，这是一种已知的抗黑色素瘤药物。与 Ova 接种的对照组相比，野生型小鼠接种 oxOva 后再接种同源 B16F10 Ova 表达黑色素瘤细胞，显示出更多的 T 细胞数量和激活、更少的肿瘤负担以及更高数量的抗原呈递细胞。使用质谱分析 oxOva 确定了三个富含氧化修饰的热点区域，这些区域与 T 细胞激活增加有关。使用 Ova 作为模型蛋白，这些发现表明多 ROS/RNS 修饰具有免疫调节作用，可能为炎症研究和肿瘤学中的疫苗接种策略开辟新的研究思路。
