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Young Thrombosis Researchers Exchange Grant: Scientific Reports

Scientific Reports from previous grantees of the Young Thrombosis Researchers Group



Effects of the proinflammatory cytokine interleukin-33 on tissue factor expression and activity in monocyte subsets in vitro – possible impact on coagulation capacity of whole blood

Author:

Stefan Stojkovic, MD

Supervisors:

Prof. MD, PhD, FESC Agneta Siegbahn
PhD MSc Pharm. Mikael Åberg
Prof. Dr. Johann Wojta

Report:

I am a PhD-Student at the Medical University of Vienna, in the research group of Prof. Johann Wojta. With the “Lab Exchange Grant” from the ESC Working Group on Thrombosis, I was able to work at the University of Uppsala, Sweden, under the supervision of Prof. Dr. Agneta Siegbahn. Agneta Siegbahn is one of the leading scientists in the field of thrombosis and tissue factor (TF) signalling. The “Lab Exchange Grant” of the ESC Working group on Thrombosis made possible the cooperation between our research groups and led to further exchange of knowledge and experience between these two groups in the field of atherosclerosis and thrombosis.

The present study, funded by “Lab Exchange Grant” of the ESC Working Group on Thrombosis, provides further insight into the interplay between inflammation and thrombosis. We could show that human monocyte subsets differently express the receptor for IL-33, ST2, a member of the Toll-like receptor/IL-1-receptor superfamily, on their surface. In particular, we demonstrated that intermediate monocytes (IM) and non-classical monocytes (NCM) express much higher levels of ST2 than classical monocytes (CM). These results delineate a differential expression of ST2 within cells of the innate immune system and provide further insight into the pro-inflammatory activation of IM and NCM. Monocytes are the predominant source of circulating, blood-borne TF and monocytes of ACS patients show high TF expression and contribute to the propagation of coagulation upon plaque rupture. Here we could show that the proinflammatory cytokine IL-33 induces differential TF mRNA and protein
expression, as well as TF activity in human monocyte subsets in an ST2/NFkB-dependent manner in vitro and ex vivo. In addition, IL-33 induces the release of procoagulant microvesicles from human monocytes in vitro and ex vivo. In a previous study of our group, we showed that circulating levels of IL-33 are associated with mortality of ACS patients. Thus, we propose a possible mechanism for IL-33 to contribute to formation of a prothrombotic state characteristic for ACS.

Results of this study were presented at the Eurothrombosis Summit 2015 in Como, Italy in form of a poster presentation. We also currently prepare a manuscript entitled “Effects of IL-33 on tissue factor expression in human monocyte subsets” for publication, and the support of the “Lab Exchange Grant” of the ESC Working group on Thrombosis will be acknowledged.

Dr. Stefan Stojkovic
15.01.2016, Vienna