Neutrophil adhesion to vessel walls impairs pulmonary circulation in COVID-19 pathology

Microthrombus formation is associated with COVID-19 severity; however, the detailed mechanism remains unclear. In this study, we investigated mouse models with severe pneumonia caused by SARS-CoV-2 infection by using our in vivo two-photon imaging system. In the lungs of SARS-CoV-2-infected mice, in...

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Published inNature communications Vol. 16; no. 1; pp. 455 - 17
Main Authors Ueki, Hiroshi, Wang, I-Hsuan, Kiso, Maki, Horie, Kenta, Iida, Shun, Mine, Sohtaro, Ujie, Michiko, Hsu, Hung-Wei, Wu, Chen-Hui Henry, Imai, Masaki, Suzuki, Tadaki, Kamitani, Wataru, Kawakami, Eiryo, Kawaoka, Yoshihiro
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 13.01.2025
Nature Publishing Group
Nature Portfolio
Subjects
13/31
13/51
14/34
14/69
45/91
59
631/326/596/4130
64/60
692/420/254
Adhesion
Animal models
Animals
Blood levels
CD44 antigen
Cell Adhesion
Cell adhesion molecules
COVID-19
COVID-19 - pathology
COVID-19 - physiopathology
COVID-19 - virology
Disease Models, Animal
Female
Humanities and Social Sciences
Humans
Hyaluronan Receptors - metabolism
Imaging techniques
In vivo methods and tests
Leukocytes (mononuclear)
Leukocytes (neutrophilic)
Lung - blood supply
Lung - pathology
Lungs
Male
Mice
Mice, Inbred C57BL
multidisciplinary
Neutrophils
Neutrophils - metabolism
Neutrophils - pathology
Perfusion
Peripheral blood mononuclear cells
Photons
Platelet Aggregation
Platelets
Pulmonary circulation
Pulmonary Circulation - physiology
SARS-CoV-2
Science
Science (multidisciplinary)
Severe acute respiratory syndrome coronavirus 2
Online AccessGet full text
ISSN2041-1723
2041-1723
DOI10.1038/s41467-024-55272-0

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Abstract Microthrombus formation is associated with COVID-19 severity; however, the detailed mechanism remains unclear. In this study, we investigated mouse models with severe pneumonia caused by SARS-CoV-2 infection by using our in vivo two-photon imaging system. In the lungs of SARS-CoV-2-infected mice, increased expression of adhesion molecules in intravascular neutrophils prolonged adhesion time to the vessel wall, resulting in platelet aggregation and impaired lung perfusion. Re-analysis of scRNA-seq data from peripheral blood mononuclear cells from COVID-19 cases revealed increased expression levels of CD44 and SELL in neutrophils in severe COVID-19 cases compared to a healthy group, consistent with our observations in the mouse model. These findings suggest that pulmonary perfusion defects caused by neutrophil adhesion to pulmonary vessels contribute to COVID-19 severity. COVID-19 severity is linked to microthrombus formation. Here, using an in vivo two-photon imaging technique in mice and human scRNA-Seq data, the authors show increased adhesion molecules on vascular neutrophils leading to platelet aggregation and reduced lung perfusion.
AbstractList Microthrombus formation is associated with COVID-19 severity; however, the detailed mechanism remains unclear. In this study, we investigated mouse models with severe pneumonia caused by SARS-CoV-2 infection by using our in vivo two-photon imaging system. In the lungs of SARS-CoV-2-infected mice, increased expression of adhesion molecules in intravascular neutrophils prolonged adhesion time to the vessel wall, resulting in platelet aggregation and impaired lung perfusion. Re-analysis of scRNA-seq data from peripheral blood mononuclear cells from COVID-19 cases revealed increased expression levels of CD44 and SELL in neutrophils in severe COVID-19 cases compared to a healthy group, consistent with our observations in the mouse model. These findings suggest that pulmonary perfusion defects caused by neutrophil adhesion to pulmonary vessels contribute to COVID-19 severity. COVID-19 severity is linked to microthrombus formation. Here, using an in vivo two-photon imaging technique in mice and human scRNA-Seq data, the authors show increased adhesion molecules on vascular neutrophils leading to platelet aggregation and reduced lung perfusion.
Microthrombus formation is associated with COVID-19 severity; however, the detailed mechanism remains unclear. In this study, we investigated mouse models with severe pneumonia caused by SARS-CoV-2 infection by using our in vivo two-photon imaging system. In the lungs of SARS-CoV-2-infected mice, increased expression of adhesion molecules in intravascular neutrophils prolonged adhesion time to the vessel wall, resulting in platelet aggregation and impaired lung perfusion. Re-analysis of scRNA-seq data from peripheral blood mononuclear cells from COVID-19 cases revealed increased expression levels of CD44 and SELL in neutrophils in severe COVID-19 cases compared to a healthy group, consistent with our observations in the mouse model. These findings suggest that pulmonary perfusion defects caused by neutrophil adhesion to pulmonary vessels contribute to COVID-19 severity.
Abstract Microthrombus formation is associated with COVID-19 severity; however, the detailed mechanism remains unclear. In this study, we investigated mouse models with severe pneumonia caused by SARS-CoV-2 infection by using our in vivo two-photon imaging system. In the lungs of SARS-CoV-2-infected mice, increased expression of adhesion molecules in intravascular neutrophils prolonged adhesion time to the vessel wall, resulting in platelet aggregation and impaired lung perfusion. Re-analysis of scRNA-seq data from peripheral blood mononuclear cells from COVID-19 cases revealed increased expression levels of CD44 and SELL in neutrophils in severe COVID-19 cases compared to a healthy group, consistent with our observations in the mouse model. These findings suggest that pulmonary perfusion defects caused by neutrophil adhesion to pulmonary vessels contribute to COVID-19 severity.
Microthrombus formation is associated with COVID-19 severity; however, the detailed mechanism remains unclear. In this study, we investigated mouse models with severe pneumonia caused by SARS-CoV-2 infection by using our in vivo two-photon imaging system. In the lungs of SARS-CoV-2-infected mice, increased expression of adhesion molecules in intravascular neutrophils prolonged adhesion time to the vessel wall, resulting in platelet aggregation and impaired lung perfusion. Re-analysis of scRNA-seq data from peripheral blood mononuclear cells from COVID-19 cases revealed increased expression levels of CD44 and SELL in neutrophils in severe COVID-19 cases compared to a healthy group, consistent with our observations in the mouse model. These findings suggest that pulmonary perfusion defects caused by neutrophil adhesion to pulmonary vessels contribute to COVID-19 severity.Microthrombus formation is associated with COVID-19 severity; however, the detailed mechanism remains unclear. In this study, we investigated mouse models with severe pneumonia caused by SARS-CoV-2 infection by using our in vivo two-photon imaging system. In the lungs of SARS-CoV-2-infected mice, increased expression of adhesion molecules in intravascular neutrophils prolonged adhesion time to the vessel wall, resulting in platelet aggregation and impaired lung perfusion. Re-analysis of scRNA-seq data from peripheral blood mononuclear cells from COVID-19 cases revealed increased expression levels of CD44 and SELL in neutrophils in severe COVID-19 cases compared to a healthy group, consistent with our observations in the mouse model. These findings suggest that pulmonary perfusion defects caused by neutrophil adhesion to pulmonary vessels contribute to COVID-19 severity.
Microthrombus formation is associated with COVID-19 severity; however, the detailed mechanism remains unclear. In this study, we investigated mouse models with severe pneumonia caused by SARS-CoV-2 infection by using our in vivo two-photon imaging system. In the lungs of SARS-CoV-2-infected mice, increased expression of adhesion molecules in intravascular neutrophils prolonged adhesion time to the vessel wall, resulting in platelet aggregation and impaired lung perfusion. Re-analysis of scRNA-seq data from peripheral blood mononuclear cells from COVID-19 cases revealed increased expression levels of CD44 and SELL in neutrophils in severe COVID-19 cases compared to a healthy group, consistent with our observations in the mouse model. These findings suggest that pulmonary perfusion defects caused by neutrophil adhesion to pulmonary vessels contribute to COVID-19 severity.COVID-19 severity is linked to microthrombus formation. Here, using an in vivo two-photon imaging technique in mice and human scRNA-Seq data, the authors show increased adhesion molecules on vascular neutrophils leading to platelet aggregation and reduced lung perfusion.
ArticleNumber 455
Author Suzuki, Tadaki
Kawakami, Eiryo
Mine, Sohtaro
Ujie, Michiko
Ueki, Hiroshi
Iida, Shun
Hsu, Hung-Wei
Kiso, Maki
Wang, I-Hsuan
Kawaoka, Yoshihiro
Kamitani, Wataru
Imai, Masaki
Horie, Kenta
Wu, Chen-Hui Henry
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SSID ssj0000391844
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Snippet Microthrombus formation is associated with COVID-19 severity; however, the detailed mechanism remains unclear. In this study, we investigated mouse models with...
Abstract Microthrombus formation is associated with COVID-19 severity; however, the detailed mechanism remains unclear. In this study, we investigated mouse...
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Adhesion
Animal models
Animals
Blood levels
CD44 antigen
Cell Adhesion
Cell adhesion molecules
COVID-19
COVID-19 - pathology
COVID-19 - physiopathology
COVID-19 - virology
Disease Models, Animal
Female
Humanities and Social Sciences
Humans
Hyaluronan Receptors - metabolism
Imaging techniques
In vivo methods and tests
Leukocytes (mononuclear)
Leukocytes (neutrophilic)
Lung - blood supply
Lung - pathology
Lungs
Male
Mice
Mice, Inbred C57BL
multidisciplinary
Neutrophils
Neutrophils - metabolism
Neutrophils - pathology
Perfusion
Peripheral blood mononuclear cells
Photons
Platelet Aggregation
Platelets
Pulmonary circulation
Pulmonary Circulation - physiology
SARS-CoV-2
Science
Science (multidisciplinary)
Severe acute respiratory syndrome coronavirus 2
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Title Neutrophil adhesion to vessel walls impairs pulmonary circulation in COVID-19 pathology
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