Role of thrombin-activatable fibrinolysis inhibitor in allergic bronchial asthma

Lung. 2012 Apr;190(2):189-98. doi: 10.1007/s00408-011-9337-9. Epub 2011 Oct 25.


Background: Bronchial asthma is an inflammatory disease of the airways. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a carboxypeptidase that besides inhibiting fibrinolysis, also regulates inflammatory processes. The only validated substrate known for TAFI is fibrin. In the present study we evaluated the role of TAFI in bronchial asthma by comparing the development of allergic bronchial asthma between wild-type (WT) and TAFI-deficient mice (KO).

Methods: Asthmatic inflammation was induced by sensitization and challenge with ovalbumin in WT (WT/OVA) and TAFI KO (KO/OVA) mice. WT mice (WT/SAL) and TAFI KO (KO/SAL) were used as controls. Cytokines, markers of inflammation, and coagulation were measured in bronchoalveolar lavage fluid (BALF).

Results: Airway hyperresponsiveness was worse in KO/OVA mice than in WT/OVA mice or control mice. Markers of lung injury were significantly increased in BALF from KO/OVA mice compared to WT/OVA mice. Airway hyperresponsiveness and the BALF concentrations of IL-5 and osteopontin were significantly increased in KO/OVA mice compared to WT/OVA mice. Treatment of WT/OVA and KO/OVA mice with a C5a receptor antagonist significantly decreased hyperresponsiveness along with the BALF concentrations of total protein and C5a compared to untreated asthmatic mice.

Conclusion: The results of this study suggest that TAFI plays a protective role in the pathogenesis of allergic inflammation probably by inhibiting the complement system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Airway Resistance
  • Animals
  • Asthma / enzymology
  • Asthma / immunology*
  • Biomarkers / chemistry
  • Blood Coagulation
  • Bronchial Hyperreactivity / immunology*
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / immunology
  • Carboxypeptidase B2 / deficiency
  • Carboxypeptidase B2 / metabolism*
  • Complement C5a / immunology
  • Fibrinolysis
  • Interleukin-5 / analysis
  • Interleukin-5 / metabolism
  • L-Lactate Dehydrogenase / blood
  • Lung Injury / immunology
  • Lung Injury / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Osteopontin / metabolism
  • Ovalbumin / immunology
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Receptors, Complement / antagonists & inhibitors


  • Biomarkers
  • Interleukin-5
  • Plasminogen Activator Inhibitor 1
  • Receptors, Complement
  • Osteopontin
  • Complement C5a
  • Ovalbumin
  • L-Lactate Dehydrogenase
  • Carboxypeptidase B2