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Intravital imaging of three different microvascular beds in SARS-CoV-2–infected mice
Severe acute respiratory syndrome coronavirus–2 (SARS-CoV-2) enters the respiratory tract, where it infects the alveoli epithelial lining. However, patients have sequelae that extend well beyond the alveoli into the pulmonary vasculature and, perhaps, beyond to the brain and other organs. Because of...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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The American Society of Hematology
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10284260/ https://www.ncbi.nlm.nih.gov/pubmed/37307197 http://dx.doi.org/10.1182/bloodadvances.2022009430 |
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author | Castanheira, Fernanda V. S. Nguyen, Rita Willson, Michelle Davoli-Ferreira, Marcela David, Bruna A. Kelly, Margaret M. Lee, Woo-Yong Kratofil, Rachel M. Zhang, Wen X. Bui-Marinos, Maxwell Corcoran, Jennifer A. Kubes, Paul |
author_facet | Castanheira, Fernanda V. S. Nguyen, Rita Willson, Michelle Davoli-Ferreira, Marcela David, Bruna A. Kelly, Margaret M. Lee, Woo-Yong Kratofil, Rachel M. Zhang, Wen X. Bui-Marinos, Maxwell Corcoran, Jennifer A. Kubes, Paul |
author_sort | Castanheira, Fernanda V. S. |
collection | PubMed |
description | Severe acute respiratory syndrome coronavirus–2 (SARS-CoV-2) enters the respiratory tract, where it infects the alveoli epithelial lining. However, patients have sequelae that extend well beyond the alveoli into the pulmonary vasculature and, perhaps, beyond to the brain and other organs. Because of the dynamic events within blood vessels, histology does not report platelet and neutrophil behavior. Because of the rapid nontranscriptional response of these cells, neither single-cell RNA sequencing nor proteomics report robustly on their critical behaviors. We used intravital microscopy in level-3 containment to examine the pathogenesis of SARS-CoV-2 within 3 organs in mice expressing human angiotensin converting enzyme 2 (ACE-2) ubiquitously (CAG-AC-70) or on epithelium (K18-promoter). Using a neon-green SARS-CoV-2, we observed both the epithelium and endothelium infected in AC70 mice but only the epithelium in K18 mice. There were increased neutrophils in the microcirculation but not in the alveoli of the lungs of AC70 mice. Platelets formed large aggregates in the pulmonary capillaries. Despite only neurons being infected within the brain, profound neutrophil adhesion forming the nidus of large platelet aggregates were observed in the cerebral microcirculation, with many nonperfused microvessels. Neutrophils breached the brain endothelial layer associated with a significant disruption of the blood-brain-barrier. Despite ubiquitous ACE-2 expression, CAG-AC-70 mice had very small increases in blood cytokine, no increase in thrombin, no infected circulating cells, and no liver involvement suggesting limited systemic effects. In summary, our imaging of SARS-CoV-2–infected mice gave direct evidence that there is a significant perturbation locally in the lung and brain microcirculation induced by local viral infection leading to increased local inflammation and thrombosis in these organs. |
format | Online Article Text |
id | pubmed-10284260 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The American Society of Hematology |
record_format | MEDLINE/PubMed |
spelling | pubmed-102842602023-06-22 Intravital imaging of three different microvascular beds in SARS-CoV-2–infected mice Castanheira, Fernanda V. S. Nguyen, Rita Willson, Michelle Davoli-Ferreira, Marcela David, Bruna A. Kelly, Margaret M. Lee, Woo-Yong Kratofil, Rachel M. Zhang, Wen X. Bui-Marinos, Maxwell Corcoran, Jennifer A. Kubes, Paul Blood Adv Immunobiology and Immunotherapy Severe acute respiratory syndrome coronavirus–2 (SARS-CoV-2) enters the respiratory tract, where it infects the alveoli epithelial lining. However, patients have sequelae that extend well beyond the alveoli into the pulmonary vasculature and, perhaps, beyond to the brain and other organs. Because of the dynamic events within blood vessels, histology does not report platelet and neutrophil behavior. Because of the rapid nontranscriptional response of these cells, neither single-cell RNA sequencing nor proteomics report robustly on their critical behaviors. We used intravital microscopy in level-3 containment to examine the pathogenesis of SARS-CoV-2 within 3 organs in mice expressing human angiotensin converting enzyme 2 (ACE-2) ubiquitously (CAG-AC-70) or on epithelium (K18-promoter). Using a neon-green SARS-CoV-2, we observed both the epithelium and endothelium infected in AC70 mice but only the epithelium in K18 mice. There were increased neutrophils in the microcirculation but not in the alveoli of the lungs of AC70 mice. Platelets formed large aggregates in the pulmonary capillaries. Despite only neurons being infected within the brain, profound neutrophil adhesion forming the nidus of large platelet aggregates were observed in the cerebral microcirculation, with many nonperfused microvessels. Neutrophils breached the brain endothelial layer associated with a significant disruption of the blood-brain-barrier. Despite ubiquitous ACE-2 expression, CAG-AC-70 mice had very small increases in blood cytokine, no increase in thrombin, no infected circulating cells, and no liver involvement suggesting limited systemic effects. In summary, our imaging of SARS-CoV-2–infected mice gave direct evidence that there is a significant perturbation locally in the lung and brain microcirculation induced by local viral infection leading to increased local inflammation and thrombosis in these organs. The American Society of Hematology 2023-06-14 /pmc/articles/PMC10284260/ /pubmed/37307197 http://dx.doi.org/10.1182/bloodadvances.2022009430 Text en © 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Immunobiology and Immunotherapy Castanheira, Fernanda V. S. Nguyen, Rita Willson, Michelle Davoli-Ferreira, Marcela David, Bruna A. Kelly, Margaret M. Lee, Woo-Yong Kratofil, Rachel M. Zhang, Wen X. Bui-Marinos, Maxwell Corcoran, Jennifer A. Kubes, Paul Intravital imaging of three different microvascular beds in SARS-CoV-2–infected mice |
title | Intravital imaging of three different microvascular beds in SARS-CoV-2–infected mice |
title_full | Intravital imaging of three different microvascular beds in SARS-CoV-2–infected mice |
title_fullStr | Intravital imaging of three different microvascular beds in SARS-CoV-2–infected mice |
title_full_unstemmed | Intravital imaging of three different microvascular beds in SARS-CoV-2–infected mice |
title_short | Intravital imaging of three different microvascular beds in SARS-CoV-2–infected mice |
title_sort | intravital imaging of three different microvascular beds in sars-cov-2–infected mice |
topic | Immunobiology and Immunotherapy |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10284260/ https://www.ncbi.nlm.nih.gov/pubmed/37307197 http://dx.doi.org/10.1182/bloodadvances.2022009430 |
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