School of Public Health, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China.
Centre for Immunology and Infection, Hong Kong Science Park, Hong Kong SAR, China.
Clin Infect Dis. 2022 Jan 29;74(2):199-209. doi: 10.1093/cid/ciab406.
The coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to threaten public health globally. Patients with severe COVID-19 disease progress to acute respiratory distress syndrome, with respiratory and multiple organ failure. It is believed that dysregulated production of proinflammatory cytokines and endothelial dysfunction contribute to the pathogenesis of severe diseases. However, the mechanisms of SARS-CoV-2 pathogenesis and the role of endothelial cells are poorly understood.
Well-differentiated human airway epithelial cells were used to explore cytokine and chemokine production after SARS-CoV-2 infection. We measured the susceptibility to infection, immune response, and expression of adhesion molecules in human pulmonary microvascular endothelial cells (HPMVECs) exposed to conditioned medium from infected epithelial cells. The effect of imatinib on HPMVECs exposed to conditioned medium was evaluated.
We demonstrated the production of interleukin-6, interferon gamma-induced protein-10, and monocyte chemoattractant protein-1 from the infected human airway cells after infection with SARS-CoV-2. Although HPMVECs did not support productive replication of SARS-CoV-2, treatment of HPMVECs with conditioned medium collected from infected airway cells induced an upregulation of proinflammatory cytokines, chemokines, and vascular adhesion molecules. Imatinib inhibited the upregulation of these cytokines, chemokines, and adhesion molecules in HPMVECs treated with conditioned medium.
We evaluated the role of endothelial cells in the development of clinical disease caused by SARS-CoV-2 and the importance of endothelial cell-epithelial cell interaction in the pathogenesis of human COVID-19 diseases.
由新型严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）引起的 2019 年冠状病毒病（COVID-19）大流行继续在全球范围内威胁着公众健康。患有严重 COVID-19 疾病的患者会发展为急性呼吸窘迫综合征，出现呼吸和多器官衰竭。人们认为，促炎细胞因子的失调产生和内皮功能障碍导致了严重疾病的发病机制。然而，SARS-CoV-2 的发病机制以及内皮细胞的作用机制仍知之甚少。
使用分化良好的人呼吸道上皮细胞来探索 SARS-CoV-2 感染后细胞因子和趋化因子的产生。我们测量了感染上皮细胞的条件培养基暴露的人肺微血管内皮细胞（HPMVEC）的易感性、免疫反应和粘附分子表达。评估了伊马替尼对暴露于条件培养基的 HPMVEC 的作用。
我们证明了 SARS-CoV-2 感染后，受感染的人呼吸道细胞产生白细胞介素 6、干扰素 γ 诱导蛋白 10 和单核细胞趋化蛋白 1。尽管 HPMVEC 不能支持 SARS-CoV-2 的有效复制，但用来自感染的气道细胞的条件培养基处理 HPMVEC 会诱导促炎细胞因子、趋化因子和血管粘附分子的上调。伊马替尼抑制了用条件培养基处理的 HPMVEC 中这些细胞因子、趋化因子和粘附分子的上调。
我们评估了内皮细胞在 SARS-CoV-2 引起的临床疾病发展中的作用以及内皮细胞-上皮细胞相互作用在人类 COVID-19 疾病发病机制中的重要性。
