Clin Infect Dis . Role of epithelial-endothelial cell interaction in the pathogenesis of SARS-CoV-2 infection

[tetano]

Clin Infect Dis


. 2021 May 6;ciab406.
doi: 10.1093/cid/ciab406. Online ahead of print.
Role of epithelial-endothelial cell interaction in the pathogenesis of SARS-CoV-2 infection


Kenrie Pui-Yan Hui ^{1 2} , Man-Chun Cheung ¹ , Ka-Ling Lai ¹ , Ka-Chun Ng ¹ , John Chi-Wang Ho ¹ , Malik Peiris ^{1 2} , John Malcolm Nicholls ³ , Michael Chi-Wai Chan ^{1 2}



Affiliations

• PMID: 33956935
• DOI: 10.1093/cid/ciab406

Abstract

Background: The 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 pro-inflammatory 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.
Methods: Well-differentiated human airway epithelial cells were used to explore the 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.
Results: We demonstrated the production of IL-6, IP-10 and MCP-1 from the infected human airway cells after infection with SARS-CoV-2. Although human pulmonary microvascular endothelial cells (HPMVECs) did not support productive replication of SARS-CoV-2, treatment of HPMVECs with conditioned medium collected from infected airway cells induced an up-regulation of pro-inflammatory cytokines, chemokines and vascular adhesion molecules. Imatinib inhibited the up-regulation of these cytokines, chemokines and adhesion molecules in HPMVECs treated with conditioned medium.
Conclusions: This study evaluates 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.

Keywords: COVID-19; SARS-CoV-2; airway epithelial cells; pathogenesis; vascular endothelial cells.