von Willebrand factor links primary hemostasis to innate immunity.

Autor: Drakeford C; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Science (PBS), Royal College of Surgeons in Ireland, Dublin, Ireland., Aguila S; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Science (PBS), Royal College of Surgeons in Ireland, Dublin, Ireland.; Centro Regional de Hemodonación, Hospital Universitario Morales Meseguer, IMIB-Arrixaca, Murcia, Spain., Roche F; Smurfit Institute of Genetics, School of Genetics and Microbiology, Trinity College Dublin, College Green, Dublin, Ireland., Hokamp K; Smurfit Institute of Genetics, School of Genetics and Microbiology, Trinity College Dublin, College Green, Dublin, Ireland., Fazavana J; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Science (PBS), Royal College of Surgeons in Ireland, Dublin, Ireland., Cervantes MP; School of Pharmacy and Biomolecular Science (PBS) and Tissue Engineering Research Group (TERG), Royal College of Surgeons in Ireland, Dublin, 2, Ireland., Curtis AM; School of Pharmacy and Biomolecular Science (PBS) and Tissue Engineering Research Group (TERG), Royal College of Surgeons in Ireland, Dublin, 2, Ireland., Hawerkamp HC; School of Medicine, Trinity College Dublin, Dublin, 2, Ireland., Dhami SPS; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Science (PBS), Royal College of Surgeons in Ireland, Dublin, Ireland., Charles-Messance H; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland., Hackett EE; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland., Chion A; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Science (PBS), Royal College of Surgeons in Ireland, Dublin, Ireland., Ward S; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Science (PBS), Royal College of Surgeons in Ireland, Dublin, Ireland., Ahmad A; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Science (PBS), Royal College of Surgeons in Ireland, Dublin, Ireland., Schoen I; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Science (PBS), Royal College of Surgeons in Ireland, Dublin, Ireland., Breen E; Department of Clinical Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland., Keane J; School of Medicine, Trinity College Dublin, Dublin, 2, Ireland., Murphy R; Department of Cardiology, St James's Hospital, Dublin, Ireland., Preston RJS; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Science (PBS), Royal College of Surgeons in Ireland, Dublin, Ireland., O'Sullivan JM; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Science (PBS), Royal College of Surgeons in Ireland, Dublin, Ireland., Sheedy FJ; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland., Fallon P; School of Medicine, Trinity College Dublin, Dublin, 2, Ireland.; Department of Cardiology, St James's Hospital, Dublin, Ireland., O'Donnell JS; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Science (PBS), Royal College of Surgeons in Ireland, Dublin, Ireland. jamesodonnell@rcsi.ie.; National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland. jamesodonnell@rcsi.ie.; National Coagulation Centre, St James's Hospital, Dublin, Ireland. jamesodonnell@rcsi.ie.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Nov 03; Vol. 13 (1), pp. 6320. Date of Electronic Publication: 2022 Nov 03.
DOI: 10.1038/s41467-022-33796-7
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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