Constitutive interaction between neutrophils and von Willebrand factor in peripheral blood

Abstract Neutrophils are known to be able to recruit von Willebrand factor (VWF) through Neutrophil Extracellular Traps (NETs) during inflammation. However, the interaction between neutrophils with plasma VWF at physiological condition remains poorly understood. In this study, we demonstrate that pe...

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Main Authors: Yan Wan, Min Gao, Jueyi Zhu, Qingqing Mu, Yue Pan, Yifan Chen, Ting Yang, Wei Deng
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-10321-6
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author Yan Wan
Min Gao
Jueyi Zhu
Qingqing Mu
Yue Pan
Yifan Chen
Ting Yang
Wei Deng
author_facet Yan Wan
Min Gao
Jueyi Zhu
Qingqing Mu
Yue Pan
Yifan Chen
Ting Yang
Wei Deng
author_sort Yan Wan
collection DOAJ
description Abstract Neutrophils are known to be able to recruit von Willebrand factor (VWF) through Neutrophil Extracellular Traps (NETs) during inflammation. However, the interaction between neutrophils with plasma VWF at physiological condition remains poorly understood. In this study, we demonstrate that peripheral neutrophils constitutively carry surface-bound VWF in a NETs-independent manner. Depletion of peripheral neutrophils in mice elevated plasma VWF levels without affecting its synthesis or secretion. A similar interaction in human blood was also observed as demonstrated from the analysis of 23 healthy human donors. Human VWF binding to neutrophils is independent of gender and age; however, individuals with non-O blood types exhibit significantly lower VWF levels on neutrophils compared to those with type O blood. Furthermore, we found that the isolated human neutrophils bind stronger to the neuraminidase-treated VWF than untreated VWF. PSGL-1 and β2-integrins, two neutrophil membrane receptors, seemingly mediate this interaction since antibodies targeting both receptors showed a significant attenuating role here. These findings suggest a constitutive interaction between neutrophils and VWF in peripheral blood, in which the desialylation VWF seems play a major role here. Both PSGL-1 and β2-integrins receptors on neutrophil contribute to this interaction. Our study reveals a function of neutrophils beyond their established antimicrobial roles.
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spelling doaj-art-115be835767f4e75bac1af9f015c2d5c2025-08-20T03:46:00ZengNature PortfolioScientific Reports2045-23222025-07-0115111210.1038/s41598-025-10321-6Constitutive interaction between neutrophils and von Willebrand factor in peripheral bloodYan Wan0Min Gao1Jueyi Zhu2Qingqing Mu3Yue Pan4Yifan Chen5Ting Yang6Wei Deng7Cyrus Tang Medical Institute and Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Soochow UniversityCyrus Tang Medical Institute and Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Soochow UniversityCyrus Tang Medical Institute and Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Soochow UniversityCyrus Tang Medical Institute and Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Soochow UniversityCyrus Tang Medical Institute and Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Soochow UniversityFujian Medical UniversityThe Second Department of Hematology, Binhai Campus of the First Affiliated Hospital, National Regional Medical Center, Fujian Medical UniversityCyrus Tang Medical Institute and Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Soochow UniversityAbstract Neutrophils are known to be able to recruit von Willebrand factor (VWF) through Neutrophil Extracellular Traps (NETs) during inflammation. However, the interaction between neutrophils with plasma VWF at physiological condition remains poorly understood. In this study, we demonstrate that peripheral neutrophils constitutively carry surface-bound VWF in a NETs-independent manner. Depletion of peripheral neutrophils in mice elevated plasma VWF levels without affecting its synthesis or secretion. A similar interaction in human blood was also observed as demonstrated from the analysis of 23 healthy human donors. Human VWF binding to neutrophils is independent of gender and age; however, individuals with non-O blood types exhibit significantly lower VWF levels on neutrophils compared to those with type O blood. Furthermore, we found that the isolated human neutrophils bind stronger to the neuraminidase-treated VWF than untreated VWF. PSGL-1 and β2-integrins, two neutrophil membrane receptors, seemingly mediate this interaction since antibodies targeting both receptors showed a significant attenuating role here. These findings suggest a constitutive interaction between neutrophils and VWF in peripheral blood, in which the desialylation VWF seems play a major role here. Both PSGL-1 and β2-integrins receptors on neutrophil contribute to this interaction. Our study reveals a function of neutrophils beyond their established antimicrobial roles.https://doi.org/10.1038/s41598-025-10321-6
spellingShingle Yan Wan
Min Gao
Jueyi Zhu
Qingqing Mu
Yue Pan
Yifan Chen
Ting Yang
Wei Deng
Constitutive interaction between neutrophils and von Willebrand factor in peripheral blood
Scientific Reports
title Constitutive interaction between neutrophils and von Willebrand factor in peripheral blood
title_full Constitutive interaction between neutrophils and von Willebrand factor in peripheral blood
title_fullStr Constitutive interaction between neutrophils and von Willebrand factor in peripheral blood
title_full_unstemmed Constitutive interaction between neutrophils and von Willebrand factor in peripheral blood
title_short Constitutive interaction between neutrophils and von Willebrand factor in peripheral blood
title_sort constitutive interaction between neutrophils and von willebrand factor in peripheral blood
url https://doi.org/10.1038/s41598-025-10321-6
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