Role of ThrombinActivatable Fibrinolysis Inhibito

Authors: Atsushi Fujiwara Osamu Taguchi Takehiro Takagi Corina N D’AlessandroGabazza Daniel BovedaRuiz Masaaki Toda Atsushi Yasukawa Yuki Matsushima Yasushi Miyake Hiroyasu Kobayashi Tetsu Kobayashi Paloma GilBernabe Masahiro Naito Masamichi Yoshida John Morser Yoshiyuki Takei Esteban C Gabazza

Publish Date: 2011/10/25

Volume: 190, Issue: 2, Pages: 189-198

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Abstract

Bronchial asthma is an inflammatory disease of the airways Thrombinactivatable 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 wildtype WT and TAFIdeficient mice KOAsthmatic 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 BALFAirway 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 IL5 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

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