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von Willebrand factor links primary hemostasis to innate immunity

Author

Listed:
  • Clive Drakeford

    (Royal College of Surgeons in Ireland)

  • Sonia Aguila

    (Royal College of Surgeons in Ireland
    Hospital Universitario Morales Meseguer, IMIB-Arrixaca)

  • Fiona Roche

    (Trinity College Dublin, College Green)

  • Karsten Hokamp

    (Trinity College Dublin, College Green)

  • Judicael Fazavana

    (Royal College of Surgeons in Ireland)

  • Mariana P. Cervantes

    (Royal College of Surgeons in Ireland)

  • Annie M. Curtis

    (Royal College of Surgeons in Ireland)

  • Heike C. Hawerkamp

    (School of Medicine, Trinity College Dublin)

  • Sukhraj Pal Singh Dhami

    (Royal College of Surgeons in Ireland)

  • Hugo Charles-Messance

    (Trinity Biomedical Sciences Institute, Trinity College Dublin)

  • Emer E. Hackett

    (Trinity Biomedical Sciences Institute, Trinity College Dublin)

  • Alain Chion

    (Royal College of Surgeons in Ireland)

  • Soracha Ward

    (Royal College of Surgeons in Ireland)

  • Azaz Ahmad

    (Royal College of Surgeons in Ireland)

  • Ingmar Schoen

    (Royal College of Surgeons in Ireland)

  • Eamon Breen

    (Trinity Translational Medicine Institute, Trinity College Dublin)

  • Joe Keane

    (School of Medicine, Trinity College Dublin)

  • Ross Murphy

    (St James’s Hospital)

  • Roger J. S. Preston

    (Royal College of Surgeons in Ireland)

  • Jamie M. O’Sullivan

    (Royal College of Surgeons in Ireland)

  • Frederick J. Sheedy

    (Trinity Biomedical Sciences Institute, Trinity College Dublin)

  • Padraic Fallon

    (School of Medicine, Trinity College Dublin
    St James’s Hospital)

  • James S. O’Donnell

    (Royal College of Surgeons in Ireland
    Our Lady’s Children’s Hospital
    National Coagulation Centre, St James’s Hospital)

Abstract

The plasma multimeric glycoprotein von Willebrand factor (VWF) plays a critical role in primary hemostasis by tethering platelets to exposed collagen at sites of vascular injury. Recent studies have identified additional biological roles for VWF, and in particular suggest that VWF may play an important role in regulating inflammatory responses. However, the molecular mechanisms through which VWF exerts its immuno-modulatory effects remain poorly understood. In this study, we report that VWF binding to macrophages triggers downstream MAP kinase signaling, NF-κB activation and production of pro-inflammatory cytokines and chemokines. In addition, VWF binding also drives macrophage M1 polarization and shifts macrophage metabolism towards glycolysis in a p38-dependent manner. Cumulatively, our findings define an important biological role for VWF in modulating macrophage function, and thereby establish a novel link between primary hemostasis and innate immunity.

Suggested Citation

  • Clive Drakeford & Sonia Aguila & Fiona Roche & Karsten Hokamp & Judicael Fazavana & Mariana P. Cervantes & Annie M. Curtis & Heike C. Hawerkamp & Sukhraj Pal Singh Dhami & Hugo Charles-Messance & Emer, 2022. "von Willebrand factor links primary hemostasis to innate immunity," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33796-7
    DOI: 10.1038/s41467-022-33796-7
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    References listed on IDEAS

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    1. A. Phillip West & Igor E. Brodsky & Christoph Rahner & Dong Kyun Woo & Hediye Erdjument-Bromage & Paul Tempst & Matthew C. Walsh & Yongwon Choi & Gerald S. Shadel & Sankar Ghosh, 2011. "TLR signalling augments macrophage bactericidal activity through mitochondrial ROS," Nature, Nature, vol. 472(7344), pages 476-480, April.
    2. Zhengjun Gao & Yiyuan Li & Fei Wang & Tao Huang & Keqi Fan & Yu Zhang & Jiangyan Zhong & Qian Cao & Tong Chao & Junling Jia & Shuo Yang & Long Zhang & Yichuan Xiao & Ji-Yong Zhou & Xin-Hua Feng & Jin , 2017. "Mitochondrial dynamics controls anti-tumour innate immunity by regulating CHIP-IRF1 axis stability," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
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    Cited by:

    1. Tristram A. J. Ryan & Alexander Hooftman & Aisling M. Rehill & Matt D. Johansen & Eóin C. O’ Brien & Juliana E. Toller-Kawahisa & Mieszko M. Wilk & Emily A. Day & Hauke J. Weiss & Pourya Sarvari & Emi, 2023. "Dimethyl fumarate and 4-octyl itaconate are anticoagulants that suppress Tissue Factor in macrophages via inhibition of Type I Interferon," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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