ERC Advanced Investigator Grant Research Group, Institute for Physiological Chemistry, University Medical Center, Johannes Gutenberg University, Duesbergweg 6, 55128 Mainz, Germany.
Mar Drugs. 2021 Jan 27;19(2):64. doi: 10.3390/md19020064.
Inorganic polyphosphate (polyP) is a widely distributed polymer found from bacteria to animals, including marine species. This polymer exhibits morphogenetic as well as antiviral activity and releases metabolic energy after enzymatic hydrolysis also in human cells. In the pathogenesis of the coronavirus disease 2019 (COVID-19), the platelets are at the frontline of this syndrome. Platelets release a set of molecules, among them polyP. In addition, the production of airway mucus, the first line of body defense, is impaired in those patients. Therefore, in this study, amorphous nanoparticles of the magnesium salt of polyP (Mg-polyP-NP), matching the size of the coronavirus SARS-CoV-2, were prepared and loaded with the secondary plant metabolite quercetin or with dexamethasone to study their effects on the respiratory epithelium using human alveolar basal epithelial A549 cells as a model. The results revealed that both compounds embedded into the polyP nanoparticles significantly increased the steady-state-expression of the gene. This mucin species is the major mucus glycoprotein present in the secreted gel-forming mucus. The level of gene expression caused by quercetin or with dexamethasone, if caged into polyP NP, is significantly higher compared to the individual drugs alone. Both quercetin and dexamethasone did not impair the growth-supporting effect of polyP on A549 cells even at concentrations of quercetin which are cytotoxic for the cells. A possible mechanism of the effects of the two drugs together with polyP on mucin expression is proposed based on the scavenging of free oxygen species and the generation of ADP/ATP from the polyP, which is needed for the organization of the protective mucin-based mucus layer.
无机多聚磷酸盐（polyP）是一种广泛存在于从细菌到动物，包括海洋生物的聚合物。这种聚合物具有形态发生和抗病毒活性，并在酶解后释放代谢能，在人类细胞中也是如此。在 2019 年冠状病毒病（COVID-19）的发病机制中，血小板处于这种综合征的前沿。血小板释放出一组分子，其中包括 polyP。此外，这些患者的气道粘液产生，即身体防御的第一道防线，受到损害。因此，在这项研究中，制备了与冠状病毒 SARS-CoV-2 大小匹配的多聚磷酸盐（polyP）镁盐无定形纳米颗粒（Mg-polyP-NP），并负载了次生植物代谢物槲皮素或地塞米松，以研究它们对人肺泡基底上皮 A549 细胞模型的呼吸上皮的影响。结果表明，两种化合物嵌入到 polyP 纳米颗粒中，显著增加了基因的稳态表达。这种粘蛋白是分泌凝胶形成粘液中存在的主要粘液糖蛋白。如果将槲皮素或地塞米松包埋在 polyP NP 中，基因表达水平比单独使用这两种药物都要高。即使在对细胞具有细胞毒性的槲皮素浓度下，槲皮素和地塞米松都不会损害 polyP 对 A549 细胞的生长支持作用。根据 polyP 清除游离氧物质和生成 ADP/ATP 的能力，提出了两种药物与 polyP 一起对粘蛋白表达产生影响的可能机制，这是组织保护性粘蛋白为基础的粘液层所必需的。
