scholarly journals Little to no expression of angiotensin‐converting enzyme‐2 on most human peripheral blood immune cells but highly expressed on tissue macrophages

2020 ◽  
Author(s):  
Xiang Song ◽  
Wei Hu ◽  
Haibo Yu ◽  
Laura Zhao ◽  
Yeqian Zhao ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2

High expression of angiotensin-converting enzyme-2 (ACE2) on tissue macrophages that may be targeted by virus SARS-CoV-2 in COVID-19 patients

2020 ◽  
Author(s):  
Xiang Song ◽  
Wei Hu ◽  
Haibo Yu ◽  
Laura Zhao ◽  
Yeqian Zhao ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Angiotensin Converting Enzyme ◽  
Immune Cells ◽  
Alveolar Macrophages ◽  
Human Peripheral Blood ◽  
Alveolar Epithelial Cells ◽  
Host Cells ◽  
Interleukin 4 ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2

AbstractAngiotensin-converting enzyme-2 (ACE2) has been recognized as the binding receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that infects host cells, causing the development of the new coronavirus infectious disease (COVID-19). To better understand the pathogenesis of COVID-19 and build up the host anti-viral immunity, we examined the levels of ACE2 expression on different types of immune cells including tissue macrophages. Flow cytometry demonstrated that there was little to no expression of ACE2 on most of the human peripheral blood-derived immune cells including CD4+ T, CD8+ T, activated CD4+ T, activated CD8+ T, CD4+CD25+CD127low/− regulatory T cells (Tregs), Th17 cells, NKT cells, B cells, NK cells, monocytes, dendritic cells (DCs), and granulocytes. Additionally, there was no ACE2 expression (< 1%) found on platelets. Compared with interleukin-4-treated type 2 macrophages (M2), the ACE2 expression was markedly increased on the activated type 1 macrophages (M1) after the stimulation with lipopolysaccharide (LPS). Immunohistochemistry demonstrated that high expressions of ACE2 were colocalized with tissue macrophages, such as alveolar macrophages found within the lungs and Kupffer cells within livers of mice. Flow cytometry confirmed the very low level of ACE2 expression on human primary pulmonary alveolar epithelial cells. These data indicate that alveolar macrophages, as the frontline immune cells, may be directly targeted by the SARS-CoV-2 infection and therefore need to be considered for the prevention and treatment of COVID-19.

Thermodynamics of the interaction between the spike protein of severe acute respiratory syndrome- coronavirus-2 and the receptor of human angiotensin converting enzyme 2. Effects of possible ligands

2020 ◽  
Author(s):  
Cristina Garcia-Iriepa ◽  
Cecilia Hognon ◽  
Antonio Francés-Monerris ◽  
Isabel Iriepa ◽  
Tom Miclot ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Molecular Mechanisms ◽  
Molecular Design ◽  
Binding Free Energy ◽  
Transmembrane Protein ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Rational Molecular Design ◽  
Rational Evaluation

<div><p>Since the end of 2019, the coronavirus SARS-CoV-2 has caused more than 180,000 deaths all over the world, still lacking a medical treatment despite the concerns of the whole scientific community. Human Angiotensin-Converting Enzyme 2 (ACE2) was recently recognized as the transmembrane protein serving as SARS-CoV-2 entry point into cells, thus constituting the first biomolecular event leading to COVID-19 disease. Here, by means of a state-of-the-art computational approach, we propose a rational evaluation of the molecular mechanisms behind the formation of the complex and of the effects of possible ligands. Moreover, binding free energy between ACE2 and the active Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein is evaluated quantitatively, assessing the molecular mechanisms at the basis of the recognition and the ligand-induced decreased affinity. These results boost the knowledge on the molecular grounds of the SARS-CoV-2 infection and allow to suggest rationales useful for the subsequent rational molecular design to treat severe COVID-19 cases.</p></div>

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