Thrombin as a central component and modulator of inflammation

Principal investigator(s):

Description

Thrombin is a main protease in primary and secondary hemostasis. Thrombin also has pro-inflammatory effects by the action on protease-activated receptors on endothelial cells and platelets, acting as one of the central nodes for crosstalk between thrombosis and inflammation. Endothelial cell-activation induces retraction and thereby extravasation of leukocytes and plasma proteins. Platelets, the primary hemostatic cell, are loaded with inflammatory mediators, and platelets will upon thrombin-dependent activation degranulate and shape the inflammatory response. Reports have also suggested that thrombin can cleave complement proteins in vitro.

The picture of thrombin and its role in inflammation is, however, far from clear, mostly dependent on the hassle to study in whole blood since an anticoagulant that does not target thrombin or upstream pathways needs to be used.

Here, we aim to:

  1. Develop novel whole blood models for enabling the study of thrombin in human whole blood ex vivo
  2. Study the role of thrombin on complement activation
  3. Study how thrombin modules acute inflammation via the stimulation cells in the vascular system

Participants

Ekholt, Karin Medical laboratory technologist
Brekke, Ole-Lars Senior Consultant / Deputy Bodø
Pischke, Søren Researcher / Senior Consultant
Lau, Corinna Researcher
Mollnes, Tom Eirik Group leader, Professor University of Tromsø, Trondheim and Oslo
Nilsson, Per H. Researcher / Deputy Oslo