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Lung

, Volume 190, Issue 2, pp 189–198 | Cite as

Role of Thrombin-Activatable Fibrinolysis Inhibitor in Allergic Bronchial Asthma

  • Atsushi Fujiwara
  • Osamu Taguchi
  • Takehiro Takagi
  • Corina N. D’Alessandro-Gabazza
  • Daniel Boveda-Ruiz
  • Masaaki Toda
  • Atsushi Yasukawa
  • Yuki Matsushima
  • Yasushi Miyake
  • Hiroyasu Kobayashi
  • Tetsu Kobayashi
  • Paloma Gil-Bernabe
  • Masahiro Naito
  • Masamichi Yoshida
  • John Morser
  • Yoshiyuki Takei
  • Esteban C. GabazzaEmail author
Article

Abstract

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.

Keywords

Bronchial asthma Coagulation Fibrinolysis Inflammation Allergy 

Notes

Acknowledgment

The present investigation was supported by Grants-in-Aid (Nos. 18590846 and 17590788) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. JM was supported by JSPS scholarship L8020.

Conflict of interest

None.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Atsushi Fujiwara
    • 1
  • Osamu Taguchi
    • 1
  • Takehiro Takagi
    • 1
  • Corina N. D’Alessandro-Gabazza
    • 1
    • 2
  • Daniel Boveda-Ruiz
    • 2
  • Masaaki Toda
    • 2
  • Atsushi Yasukawa
    • 2
  • Yuki Matsushima
    • 2
  • Yasushi Miyake
    • 2
  • Hiroyasu Kobayashi
    • 1
  • Tetsu Kobayashi
    • 1
  • Paloma Gil-Bernabe
    • 5
  • Masahiro Naito
    • 1
  • Masamichi Yoshida
    • 3
  • John Morser
    • 4
  • Yoshiyuki Takei
    • 5
  • Esteban C. Gabazza
    • 2
    Email author
  1. 1.Department of Pulmonary and Critical Care MedicineMie University School of MedicineTsu City, Mie PrefectureJapan
  2. 2.Department of ImmunologyMie University School of MedicineTsu City, Mie PrefectureJapan
  3. 3.Mie Prefecture General Hospital, 5450-132Hinaga, Yokkaichi, MieJapan
  4. 4.Division of HematologyStanford University School of MedicineStanfordUSA
  5. 5.Department of Gastroenterology and HepatologyMie University School of MedicineTsu City, Mie PrefectureJapan

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