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Semin Thromb Hemost
DOI: 10.1055/s-0044-1782660
Review Article

The Role of Myeloid Cells in Thromboinflammatory Disease

David Noone
1   Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland
2   National Children's Research Centre, Our Lady's Children's Hospital Crumlin, Dublin, Ireland
,
Roger J.S. Preston
1   Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland
2   National Children's Research Centre, Our Lady's Children's Hospital Crumlin, Dublin, Ireland
,
Aisling M. Rehill
1   Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland
2   National Children's Research Centre, Our Lady's Children's Hospital Crumlin, Dublin, Ireland
› Author Affiliations Funding Grant support for D.N., A.M.R., and R.J.S.P. is provided by Science Foundation Ireland (21/FFP-A/8859). R.J.S.P. is supported by funding from the National Children's Research Centre (C/18/3) and Health Research Board Ireland (ILP-POR-2022-060).
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Abstract

Inflammation contributes to the development of thrombosis, but the mechanistic basis for this association remains poorly understood. Innate immune responses and coagulation pathways are activated in parallel following infection or injury, and represent an important host defense mechanism to limit pathogen spread in the bloodstream. However, dysregulated proinflammatory activity is implicated in the progression of venous thromboembolism and arterial thrombosis. In this review, we focus on the role of myeloid cells in propagating thromboinflammation in acute inflammatory conditions, such as sepsis and coronavirus disease 2019 (COVID-19), and chronic inflammatory conditions, such as obesity, atherosclerosis, and inflammatory bowel disease. Myeloid cells are considered key drivers of thromboinflammation via upregulated tissue factor activity, formation of neutrophil extracellular traps (NETs), contact pathway activation, and aberrant coagulation factor–mediated protease-activated receptor (PAR) signaling. We discuss how strategies to target the intersection between myeloid cell–mediated inflammation and activation of blood coagulation represent an exciting new approach to combat immunothrombosis. Specifically, repurposed anti-inflammatory drugs, immunometabolic regulators, and NETosis inhibitors present opportunities that have the potential to dampen immunothrombotic activity without interfering with hemostasis. Such therapies could have far-reaching benefits for patient care across many thromboinflammatory conditions.

Keywords

immunothrombosis - thromboinflammation - monocytes - macrophages - neutrophils

Authors' Contributions

All the authors were involved in writing and reviewing the article.




Publication History

Article published online:
28 March 2024

© 2024. Thieme. All rights reserved.

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