von Willebrand factor links primary hemostasis to innate immunity

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 E. Hackett, Alain Chion, Soracha Ward, Azaz Ahmad, Ingmar Schoen, Eamon Breen, Joe Keane, Ross Murphy, Roger J. S. Preston, Jamie M. O’Sullivan, Frederick J. Sheedy, Padraic Fallon and James S. O’Donnell ()
Additional contact information
Clive Drakeford: Royal College of Surgeons in Ireland
Sonia Aguila: Royal College of Surgeons in Ireland
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
James S. O’Donnell: Royal College of Surgeons in Ireland

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-33796-7

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