PDF(Pubmed)
Abstract：
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, known as coronavirus disease 2019 (COVID-19) causes cytokine release syndrome (CRS), leading to acute respiratory distress syndrome (ARDS), acute kidney and cardiac injury, liver dysfunction, and multiorgan failure. Although several studies have discussed the role of 5-lipoxygenase (5-LOX) in viral infections, such as influenzae and SARS, it remains unexplored in the pathophysiology of COVID-19. 5-LOX acts on free arachidonic acid (AA) to form proinflammatory leukotrienes (LTs). Of note, numerous cells involved with COVID-19 (e.g., inflammatory and smooth muscle cells, platelets, and vascular endothelium) widely express leukotriene receptors. Moreover, 5-LOX metabolites induce the release of cytokines (e.g., tumour necrosis factor-α [TNF-α], interleukin-1α [IL-1α], and interleukin-1β [IL-1β]) and express tissue factor on cell membranes and activate plasmin. Since macrophages, monocytes, neutrophils, and eosinophils can express lipoxygenases, activation of 5-LOX and the subsequent release of LTs may contribute to the severity of COVID-19. This review sheds light on the potential implications of 5-LOX in SARS-CoV-2-mediated infection and the anticipated therapeutic role of 5-LOX inhibitors.
摘要：
严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）感染，被称为2019年冠状病毒病（COVID-19）导致细胞因子释放综合征（CRS），导致急性呼吸窘迫综合征（ARDS），急性肾和心脏损伤，肝功能障碍,多器官衰竭。尽管一些研究已经讨论了5-脂氧合酶（5-LOX）在病毒感染中的作用，比如流感和SARS，在COVID-19的病理生理学中仍未被探索。5-LOX作用于游离花生四烯酸(AA)以形成促炎性白三烯(LTs)。值得注意的是，涉及COVID-19的许多细胞(例如，炎症和平滑肌细胞，血小板,和血管内皮）广泛表达白三烯受体。此外，5-LOX代谢物诱导细胞因子的释放(例如，肿瘤坏死因子-α[TNF-α]，白细胞介素-1α[IL-1α]，和白介素-1β[IL-1β]）并在细胞膜上表达组织因子并激活纤溶酶。因为巨噬细胞,单核细胞,中性粒细胞，嗜酸性粒细胞可以表达脂氧合酶，5-LOX的激活和随后的LTs的释放可能与COVID-19的严重程度有关。这篇综述揭示了5-LOX在SARS-CoV-2介导的感染中的潜在意义以及5-LOX抑制剂的预期治疗作用。
