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

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...

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Main Authors: Hiroshi Ueki, I-Hsuan Wang, Maki Kiso, Kenta Horie, Shun Iida, Sohtaro Mine, Michiko Ujie, Hung-Wei Hsu, Chen-Hui Henry Wu, Masaki Imai, Tadaki Suzuki, Wataru Kamitani, Eiryo Kawakami, Yoshihiro Kawaoka
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-55272-0
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author Hiroshi Ueki
I-Hsuan Wang
Maki Kiso
Kenta Horie
Shun Iida
Sohtaro Mine
Michiko Ujie
Hung-Wei Hsu
Chen-Hui Henry Wu
Masaki Imai
Tadaki Suzuki
Wataru Kamitani
Eiryo Kawakami
Yoshihiro Kawaoka
author_facet Hiroshi Ueki
I-Hsuan Wang
Maki Kiso
Kenta Horie
Shun Iida
Sohtaro Mine
Michiko Ujie
Hung-Wei Hsu
Chen-Hui Henry Wu
Masaki Imai
Tadaki Suzuki
Wataru Kamitani
Eiryo Kawakami
Yoshihiro Kawaoka
author_sort Hiroshi Ueki
collection DOAJ
description 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.
format Article
id doaj-art-7b2e63d4a60a45ee881b5cd994296751
institution Kabale University
issn 2041-1723
language English
publishDate 2025-01-01
publisher Nature Portfolio
record_format Article
series Nature Communications
spelling doaj-art-7b2e63d4a60a45ee881b5cd9942967512025-01-19T12:29:47ZengNature PortfolioNature Communications2041-17232025-01-0116111710.1038/s41467-024-55272-0Neutrophil adhesion to vessel walls impairs pulmonary circulation in COVID-19 pathologyHiroshi Ueki0I-Hsuan Wang1Maki Kiso2Kenta Horie3Shun Iida4Sohtaro Mine5Michiko Ujie6Hung-Wei Hsu7Chen-Hui Henry Wu8Masaki Imai9Tadaki Suzuki10Wataru Kamitani11Eiryo Kawakami12Yoshihiro Kawaoka13Division of Virology, Institute of Medical Science, University of TokyoInstitute of Biomedical Sciences, Academia SinicaDivision of Virology, Institute of Medical Science, University of TokyoDepartment of Artificial Intelligence Medicine, Graduate School of Medicine, Chiba UniversityDepartment of Pathology, National Institute of Infectious DiseasesDepartment of Pathology, National Institute of Infectious DiseasesDivision of Virology, Institute of Medical Science, University of TokyoInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaDivision of Virology, Institute of Medical Science, University of TokyoDepartment of Pathology, National Institute of Infectious DiseasesDepartment of Infectious Diseases and Host Defense, Gunma University Graduate School of MedicineDepartment of Artificial Intelligence Medicine, Graduate School of Medicine, Chiba UniversityDivision of Virology, Institute of Medical Science, University of TokyoAbstract 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.https://doi.org/10.1038/s41467-024-55272-0
spellingShingle Hiroshi Ueki
I-Hsuan Wang
Maki Kiso
Kenta Horie
Shun Iida
Sohtaro Mine
Michiko Ujie
Hung-Wei Hsu
Chen-Hui Henry Wu
Masaki Imai
Tadaki Suzuki
Wataru Kamitani
Eiryo Kawakami
Yoshihiro Kawaoka
Neutrophil adhesion to vessel walls impairs pulmonary circulation in COVID-19 pathology
Nature Communications
title Neutrophil adhesion to vessel walls impairs pulmonary circulation in COVID-19 pathology
title_full Neutrophil adhesion to vessel walls impairs pulmonary circulation in COVID-19 pathology
title_fullStr Neutrophil adhesion to vessel walls impairs pulmonary circulation in COVID-19 pathology
title_full_unstemmed Neutrophil adhesion to vessel walls impairs pulmonary circulation in COVID-19 pathology
title_short Neutrophil adhesion to vessel walls impairs pulmonary circulation in COVID-19 pathology
title_sort neutrophil adhesion to vessel walls impairs pulmonary circulation in covid 19 pathology
url https://doi.org/10.1038/s41467-024-55272-0
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