Alcohol Increases Lung Angiotensin-Converting Enzyme 2 Expression and Exacerbates Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein Subunit 1–Induced Acute Lung Injury in K18-hACE2 Transgenic Mice
The American Journal of Pathology
Article in Press
During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, alcohol consumption increased markedly. Nearly one in four adults reported drinking more alcohol to cope with stress. Chronic alcohol abuse is now recognized as a factor complicating the course of acute respiratory distress syndrome. and increasing mortality. To investigate the mechanisms behind this interaction, we developed a combined acute respiratory distress syndrome and chronic alcohol abuse mouse model by intratracheally instilling the S1 subunit of SARS-CoV-2 spike protein (S1SP) in K18-human angiotensin-converting enzyme 2 (ACE2) transgenic mice that express the human ACE2 receptor for SARS-CoV-2 and are kept on an ethanol diet. Seventy-two hours after S1SP instillation, mice on an ethanol diet showed a strong decrease in body weight, a dramatic increase in white blood cell content of bronchoalveolar lavage fluid, and an augmented cytokine storm, compared with S1SP-treated mice on a control diet. Histologic examination of lung tissue showed abnormal recruitment of immune cells in the alveolar space, abnormal parenchymal architecture, and worsening Ashcroft score in S1SP- and alcohol-treated animals. Along with the activation of proinflammatory biomarkers (NF-κB, STAT3, NLRP3 inflammasome), lung tissue homogenates from mice on an alcohol diet showed overexpression of ACE2 compared with mice on a control diet. This model could be useful for the development of therapeutic approaches against alcohol-exacerbated coronavirus disease 2019.
Original Publication Citation
Solopov, P. A., Colunga Biancatelli, R. M. L. C., & Catravas, J. D. (2022). Alcohol increases lung angiotensin-converting enzyme 2 expression and exacerbates severe acute respiratory syndrome coronavirus 2 spike protein subunit 1-induced acute lung injury in K18-hACE2 transgenic mice. The American Journal of Pathology, Article in press, 1-11. https://doi.org/10.1016/j.ajpath.2022.03.012
Solopov, Pavel A.; Colunga Biancatelli, Ruben Manuel Luciano; and Catravas, John D., "Alcohol Increases Lung Angiotensin-Converting Enzyme 2 Expression and Exacerbates Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein Subunit 1–Induced Acute Lung Injury in K18-hACE2 Transgenic Mice" (2022). Bioelectrics Publications. 333.
0000-0002-1705-027X (Solopov), 0000-0002-1174-3876 (Biancatelli), 0000-0002-5098-295X (Catravas)