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

Author

Listed:
  • Hiroshi Ueki

    (University of Tokyo
    National Center for Global Health and Medicine Research Institute)

  • I-Hsuan Wang

    (Academia Sinica)

  • Maki Kiso

    (University of Tokyo)

  • Kenta Horie

    (Chiba University
    Chiba University)

  • Shun Iida

    (National Institute of Infectious Diseases)

  • Sohtaro Mine

    (National Institute of Infectious Diseases)

  • Michiko Ujie

    (University of Tokyo)

  • Hung-Wei Hsu

    (Academia Sinica)

  • Chen-Hui Henry Wu

    (Academia Sinica
    National Yang Ming Chiao Tung University)

  • Masaki Imai

    (University of Tokyo
    National Center for Global Health and Medicine Research Institute)

  • Tadaki Suzuki

    (National Institute of Infectious Diseases)

  • Wataru Kamitani

    (Gunma University Graduate School of Medicine)

  • Eiryo Kawakami

    (Chiba University
    Chiba University
    RIKEN)

  • Yoshihiro Kawaoka

    (University of Tokyo
    National Center for Global Health and Medicine Research Institute
    University of Tokyo
    University of Wisconsin-Madison)

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.

Suggested Citation

  • 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 & Yo, 2025. "Neutrophil adhesion to vessel walls impairs pulmonary circulation in COVID-19 pathology," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-55272-0
    DOI: 10.1038/s41467-024-55272-0
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