Complement and TLRs in bacteria-induced coagulation

Principal investigator(s):

Description

Several studies indicate that activation of complement is involved in inflammation, tissue damage and coagulation activation in myocardial infarction, ischemic stroke and sepsis. Urinary tract infections and bacterial infections in the lungs are known risk factors for venous thromboembolism (VTE) including deep venous thrombosis (DVT) and pulmonary embolism (PE). The complement system interacts with several other cascade systems including the coagulation and the fibrinolytic systems. Both complement and coagulation are activated when the bacteria get in contact with blood in sepsis leading to inflammation and coagulation activation ranging from coagulation disturbances to disseminated intravascular coagulation (DIC). We have developed different models using fresh full human blood to study the mechanisms involved in complement induced activation of inflammation, coagulation and platelet activation. In the main model we use the anticoagulant Lepirudin which do not affect complement activation. By adding different Gram-positive and Gram-negative bacteria and specific inhibitors of complement, CD14 and TLRs we can study how complement activation and TLRs are involved in bacteria-induced inflammation, activation of coagulation and blood platelets.

Main goals:

  • Study the relative role of complement, CD14 and TLRs in bacteria-induced activation of coagulation and blood platelets
  • Study the relative role of contact activation and FXII in bacteria-induced activation of coagulation and blood platelets
  • Analyze biomarkers of complement activation and related biomarkers for inflammation in a clinical study on venous thromboembolism in cooperation with others

Participants

Brekke, Ole-Lars Senior Consultant / Deputy Bodø
Emblem, Åse Chief medical laboratory technologist
Nielsen, Erik Waage Professor / Senior Consultant
Nilsson, Per H. Researcher / Deputy Oslo
Mollnes, Tom Eirik Group leader, Professor University of Tromsø, Trondheim and Oslo