Himly Martin, Geppert Mark, Hofer Sabine, Hofstätter Norbert, Horejs-Höck Jutta, Duschl Albert
Department for Biosciences & Allergy Cancer BioNano Research Centre, University of Salzburg, Hellbrunner Strasse 34, Salzburg, 5020, Austria.
Small. 2020 May;16(21):e1907483. doi: 10.1002/smll.201907483. Epub 2020 Apr 2.
The immune system is professional in recognizing and responding to non-self, including nanomaterials. Immune responses by professional and nonprofessional immune cells are thus nearly inevitable upon exposure of cells and organisms to such materials. The state of research into taking the immune system into account in nanosafety studies is reviewed and three aspects in which further improvements are desirable are identified: 1) Due to technical limitations, more stringent testing for endotoxin contamination should be made. 2) Since under overdose conditions immunity shows unphysiological responses, all doses used should be justified by being equivalent to tissue-delivered doses. 3) When markers of acute inflammation or cell stress are observed, functional assays are necessary to distinguish between homeostatic fluctuation and genuine defensive or tolerogenic responses. Since immune activation can also indicate that the immune system considers a stimulus to be harmless and induces tolerance, activation markers by themselves do not necessarily imply a danger to the body. Guidelines such as these are necessary to approach the point where specific nanomaterials are classified as safe based on reliable testing strategies.
免疫系统擅长识别并应对非自身物质，包括纳米材料。因此，当细胞和生物体接触此类材料时，专业和非专业免疫细胞的免疫反应几乎不可避免。本文综述了纳米安全性研究中考虑免疫系统的研究现状，并确定了三个需要进一步改进的方面：1）由于技术限制，应加强对内毒素污染的检测。2）由于在过量条件下免疫会表现出非生理性反应，所有使用的剂量都应通过等同于组织给药剂量来证明其合理性。3）当观察到急性炎症或细胞应激标志物时，需要进行功能测定以区分稳态波动与真正的防御或耐受性反应。由于免疫激活也可能表明免疫系统认为刺激是无害的并诱导耐受性，因此激活标志物本身并不一定意味着对身体有危险。这些指南对于基于可靠的测试策略将特定纳米材料归类为安全的目标而言是必要的。
