Graduate Program in Biomedical Sciences, Federal University of Fronteira Sul, SC, Chapecó, Brazil.
Graduate Program in Science and Food Technology, Federal University of Fronteira Sul, Laranjeiras Do Sul, PR, Brazil.
J Mol Med (Berl). 2022 Apr;100(4):645-663. doi: 10.1007/s00109-022-02185-4. Epub 2022 Mar 6.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has significantly impacted the world and has driven many researchers into the pathophysiology of COVID-19. In the findings, there is a close association between purinergic signaling and the immune response. Then, this study aimed to evaluate alterations in the purinergic signaling in COVID-19 patients according to range severity. We divided the COVID-19 patients into moderate and severe cases following the guideless of NIH and WHO, together with clinical characteristics. The blood samples were collected to obtain PBMCs and platelets. We analyzed the ectonucleotidase activities through ATP, ADP, AMP, Ado hydrolysis, E-NTPDase1 (CD39), and 5'-NT (CD73) expression by flow cytometry in total leukocytes. The extracellular ATP was measured by bioluminescence, and cytokines were analyzed by flow cytometry. We observed a decrease in ATP hydrolysis and increased AMP hydrolysis in PBMCs for both groups. In severe cases, ATP hydrolysis was raised for the platelets, while ADP and AMP hydrolysis have risen significantly in both groups. Additionally, there was a significant increase in ADP hydrolysis in severe cases compared to moderate cases. In addition, we observed an increase in the ADA activity in platelets of moderate patients. Moderate and severe cases showed increased expression of CD39 and CD73 in total leukocytes. To finalize the purinergic signaling, extracellular ATP was increased in both groups. Furthermore, there was an increase in IL-2, IL-6, IL-10, and IL-17 in moderate and severe groups. Thus, for the first time, our findings confirm the changes in purinergic signaling and immune response in COVID-19, in addition to making it more evident that the severity range directly impacts these changes. Therefore, the therapeutic potential of the purinergic system must be highlighted and studied as a possible target for the treatment of SARS-CoV-2 disease. KEY MESSAGES: COVID-19 patients exhibit alterations in purinergic system and immune response. High levels of extracellular ATP lead to different inflammatory responses. CD39 and CD73 expression were increased in COVID-19 patients. Cytokines IL-2, IL-6, IL-10, and IL-17 also were altered in these patients. The purinergic system may be a possibility target to SARS-CoV-2 treatments.
严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 大流行对世界产生了重大影响，促使许多研究人员深入研究 COVID-19 的病理生理学。在研究结果中，嘌呤能信号与免疫反应密切相关。因此，本研究旨在根据严重程度评估 COVID-19 患者嘌呤能信号的变化。我们根据 NIH 和 WHO 的指南以及临床特征，将 COVID-19 患者分为中度和重度病例。采集血液样本以获得 PBMC 和血小板。我们通过流式细胞术分析总白细胞中的外核苷酸酶活性，通过 ATP、ADP、AMP、Ado 水解、E-NTPDase1 (CD39) 和 5'-NT (CD73) 表达。通过生物发光测量细胞外 ATP，通过流式细胞术分析细胞因子。我们观察到两组 PBMC 中的 ATP 水解减少，AMP 水解增加。在重症病例中，血小板中的 ATP 水解增加，而两组中的 ADP 和 AMP 水解均显著增加。此外，与中度病例相比，重症病例中的 ADP 水解显著增加。此外，我们观察到中度患者血小板中的 ADA 活性增加。中度和重度病例总白细胞中 CD39 和 CD73 的表达增加。为了完成嘌呤能信号，两组细胞外 ATP 均增加。此外，中度和重度组中 IL-2、IL-6、IL-10 和 IL-17 增加。因此，我们的研究结果首次证实了 COVID-19 中嘌呤能信号和免疫反应的变化，并且更明显的是，严重程度范围直接影响这些变化。因此，必须强调嘌呤能系统的治疗潜力，并将其作为 SARS-CoV-2 疾病治疗的潜在靶点进行研究。
COVID-19 患者的嘌呤能系统和免疫反应发生改变。高水平的细胞外 ATP 导致不同的炎症反应。COVID-19 患者中 CD39 和 CD73 的表达增加。这些患者的细胞因子 IL-2、IL-6、IL-10 和 IL-17 也发生了改变。嘌呤能系统可能是 SARS-CoV-2 治疗的一个潜在靶点。
