Thromb Haemost 2017; 117(07): 1379-1390
DOI: 10.1160/TH16-10-0784
Coagulation and Fibrinolysis
Schattauer GmbH

IL-33 stimulates the release of procoagulant microvesicles from human monocytes and differentially increases tissue factor in human monocyte subsets

Stefan Stojkovic
1  Department of Internal Medicine II, Medical University of Vienna, Austria
,
Åsa Thulin
2  Department of Medical Sciences, Clinical Chemistry and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
,
Lena Hell
3  Department of Internal Medicine I, Clinical Division of Hematology and Hemostaseology, Medical University of Vienna, Austria
,
Barbara Thaler
1  Department of Internal Medicine II, Medical University of Vienna, Austria
,
Sabine Rauscher
4  Core Facilities, Medical University of Vienna, Austria
,
Johanna Baumgartner
1  Department of Internal Medicine II, Medical University of Vienna, Austria
,
Marion Gröger
4  Core Facilities, Medical University of Vienna, Austria
,
Cihan Ay
3  Department of Internal Medicine I, Clinical Division of Hematology and Hemostaseology, Medical University of Vienna, Austria
,
Svitlana Demyanets
5  Department of Laboratory Medicine, Medical University of Vienna, Austria
,
Christoph Neumayer
6  Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Austria
,
Ihor Huk
6  Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Austria
,
Andreas Spittler
4  Core Facilities, Medical University of Vienna, Austria
6  Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Austria
,
Kurt Huber
7  3rd Medical Department for Cardiology and Emergency Medicine, Wilhelminen Hospital, Vienna, Austria
8  Sigmund FReud Private University, Medical School, Vienna, Austria
,
Johann Wojta
1  Department of Internal Medicine II, Medical University of Vienna, Austria
4  Core Facilities, Medical University of Vienna, Austria
8  Sigmund FReud Private University, Medical School, Vienna, Austria
9  Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna Austria
,
Agneta Siegbahn
2  Department of Medical Sciences, Clinical Chemistry and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
,
Mikael Åberg
2  Department of Medical Sciences, Clinical Chemistry and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
› Author Affiliations
Financial Support: The research was funded by the “Young Thrombosis Researcher Exchange Grant” of the Working Group on Thrombosis of European Society of Cardiology to Stefan Stojkovic; by a special programme grant of the FWF to Johann Wojta, grant number SFB54 “Cellular mediators linking inflammation and thrombosis”. Furthermore, the work was supported by the Association for the Promotion of Research in Arteriosclerosis, Thrombosis and Vascular Biology, the Swedish Research Council, grant number 2012–2579 to Agneta Siegbahn, and local funds at Uppsala University and SciLifeLab, Uppsala University, Uppsala, Sweden.
Further Information

Publication History

Received: 14 October 2016

Accepted after major revision: 05 April 2017

Publication Date:
11 November 2017 (online)

Summary

Monocytes and monocyte-derived microvesicles (MVs) are the main source of circulating tissue factor (TF). Increased monocyte TF expression and increased circulating levels of procoagulant MVs contribute to the formation of a prothrombotic state in patients with cardiovascular disease. Interleukin (IL)-33 is a pro-inflammatory cytokine involved in atherosclerosis and other inflammatory diseases, but its role in regulating thrombosis is still unclear. The aim of the present study was to investigate the effects of IL-33 on the procoagulant properties of human monocytes and monocyte-derived MVs. IL-33 induced a time- and concentration-dependent increase of monocyte TF mRNA and protein levels via binding to the ST2-receptor and activation of the NFκB-pathway. The IL-33 treated monocytes also released CD14+TF+ MVs and IL-33 was found to increase the TF activity of both the isolated monocytes and monocyte-derived MVs. The monocytes were classified into subsets according to their CD14 and CD16 expression. Intermediate monocytes (IM) showed the highest ST2 receptor expression, followed by non-classical monocytes (NCM), and classical monocytes (CM). IL-33 induced a significant increase of TF only in the IM (p<0.01), with a tendency in NCM (p=0.06), but no increase was observed in CM. Finally, plasma levels of IL–33 were positively correlated with CD14+TF+ MVs in patients undergoing carotid endarterectomy (r=0.480; p=0.032; n=20). We hereby provide novel evidence that the proinflammatory cytokine IL-33 induces differential TF expression and activity in monocyte subsets, as well as the release of procoagulant MVs. In this manner, IL-33 may contribute to the formation of a prothrombotic state characteristic for cardiovascular disease.

Supplementary Material to this article is available online at www.thrombosis-online.com.