Impaired Macrophage-Mediate Inflammation Resolution in COVID-19 Disease
Ira Tabas, Richard J. Stock Professor of Medicine (Immunology); Professor of Pathology & Cell Biology at CUMC; Vice-Chair of Research, Department of Medicine
We plan to explore the following hypothesis: down-regulation of ACE2 on type II-alveolar epithelial cells (AEC-II) and possibly macrophages by Cov2 Spike protein impairs the local production of the ACE2-derived peptide, Ang-(1-7). We propose that Ang-(1-7), by signaling through its receptor Mas, is an important local resolving mediator for macrophages in this case alveolar macrophages. Thus, the deficiency of this mediator helps spark an amplification cycle of impaired resolution and hyperinflammation, thereby promoting the progression from moderate to severe COVID-19 disease.