CC BY-NC-ND 4.0 · Thromb Haemost 2019; 119(09): 1394-1402
DOI: 10.1055/s-0039-1692219
Coagulation and Fibrinolysis
Georg Thieme Verlag KG Stuttgart · New York

Protease-Activated Receptors 1 and 3 are Differentially Expressed on Human Monocyte Subsets and are Upregulated by Lipopolysaccharide Ex Vivo and In Vivo

Barbara Thaler
1  Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
Philipp J. Hohensinner
1  Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
Johanna Baumgartner
1  Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
Patrick Haider
1  Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
Konstantin A. Krychtiuk
1  Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
Christian Schörgenhofer
2  Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
,
Bernd Jilma
2  Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
,
Lena Hell
3  Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
,
Michael B. Fischer
4  Clinic for Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria
5  Department for Health Science and Biomedicine, Danube University Krems, Krems, Austria
,
Kurt Huber
6  3rd Medical Department for Cardiology and Emergency Medicine, Wilhelminen Hospital, Vienna, Austria
,
Christian Hengstenberg
1  Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
Walter S. Speidl
1  Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
Johann Wojta
1  Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
7  Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna, Austria
8  Core Facilities, Medical University of Vienna, Vienna, Austria
› Author Affiliations
Funding This project was funded by a grant of the Austrian Science Fund FWF (SFB-54) to J.W. and W.S.S.
Further Information

Publication History

17 November 2018

29 April 2019

Publication Date:
10 July 2019 (eFirst)

  

Abstract

Monocytes are activated in inflammatory conditions via a variety of cytokine receptors as well as in a procoagulatory setting through thrombin, acting upon protease-activated receptors (PARs). This study investigated the expression pattern of PAR1 and PAR3 on human monocyte subsets. Furthermore, a possible regulation of the expression of PAR1 and PAR3 in these cells by inflammatory activation were studied. CD16+ monocytes showed significantly higher levels of PAR1 and PAR3 as compared with CD16 monocytes. Ex vivo treatment of whole blood with lipopolysaccharide (LPS) increased PAR1 and PAR3 messenger ribonucleic acid (mRNA) in human monocytes. In addition, increase of PAR1 was seen in all three subsets upon LPS treatment, whereas PAR3 increased significantly only in CD16 monocytes and nonclassical CD16+ monocytes. Protein levels of PAR1 and PAR3 significantly increased on monocytes in vivo in human endotoxemia 1 hour after LPS infusion. PAR1 increased significantly in CD16 monocytes and nonclassical CD16+ monocytes. In this in vivo model, PAR3 was also significantly elevated in CD16 monocytes and increased slightly albeit not significantly in CD16+ monocytes. Endotoxemia increased plasminogen activator inhibitor-1 (PAI-1) and tissue factor (TF) expression in monocytes in humans. Pretreatment of healthy volunteers with the PAR1 antagonist vorapaxar blocked the increase in PAI-1 but not the increase in TF. We here provide new evidence for a critical role for monocytes as cellular mediators that contribute to the activation of coagulation in diseases characterized by an inflammatory state.