Laboratory of Biochemistry, Faculty of Chemistry, National & Kapodistrian University, Athens, Greece.
Laboratory of Biology, Biochemistry and Microbiology, Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.
Biofactors. 2020 Nov;46(6):927-933. doi: 10.1002/biof.1696. Epub 2020 Dec 9.
Recent articles report elevated markers of coagulation, endothelial injury, and microthromboses in lungs from deceased COVID-19 patients. However, there has been no discussion of what may induce intravascular coagulation. Platelets are critical in the formation of thrombi and their most potent trigger is platelet activating factor (PAF), first characterized by Demopoulos and colleagues in 1979. PAF is produced by cells involved in host defense and its biological actions bear similarities with COVID-19 disease manifestations. PAF can also stimulate perivascular mast cell activation, leading to inflammation implicated in severe acute respiratory syndrome (SARS). Mast cells are plentiful in the lungs and are a rich source of PAF and of inflammatory cytokines, such as IL-1β and IL-6, which may contribute to COVID-19 and especially SARS. The histamine-1 receptor antagonist rupatadine was developed to have anti-PAF activity, and also inhibits activation of human mast cells in response to PAF. Rupatadine could be repurposed for COVID-19 prophylaxis alone or together with other PAF-inhibitors of natural origin such as the flavonoids quercetin and luteolin, which have antiviral, anti-inflammatory, and anti-PAF actions.
最近的文章报道了在死于 COVID-19 的患者的肺部中存在升高的凝血、内皮损伤和微血栓形成的标志物。然而，尚未讨论可能导致血管内凝血的原因。血小板在血栓形成中起着关键作用，其最有效的触发因素是血小板激活因子（PAF），Demopoulos 及其同事于 1979 年首次对其进行了描述。PAF 由参与宿主防御的细胞产生，其生物学作用与 COVID-19 疾病表现相似。PAF 还可以刺激血管周围肥大细胞的激活，导致与严重急性呼吸综合征（SARS）有关的炎症。肥大细胞在肺部中大量存在，是 PAF 和炎症细胞因子（如 IL-1β 和 IL-6）的丰富来源，这些细胞因子可能与 COVID-19 尤其是 SARS 有关。组胺 H1 受体拮抗剂 rupatadine 的开发具有抗 PAF 活性，并且还可以抑制 PAF 对人肥大细胞的激活。rupatadine 可以单独用于 COVID-19 的预防，也可以与其他天然来源的 PAF 抑制剂（如黄酮类 quercetin 和 luteolin）一起使用，这些抑制剂具有抗病毒、抗炎和抗 PAF 作用。
