Thrombin in the Airways of Asthmatic Patients |
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Authors: | E C Gabazza O Taguchi S Tamaki H Takeya H Kobayashi H Yasui T Kobayashi O Hataji H Urano H Zhou K Suzuki Y Adachi |
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Affiliation: | (1) Third Department of Internal Medicine, Mie University School of Medicine, Edobashi 2-174, Tsu, Mie 5148507, Japan, JP;(2) Department of Molecular Pathobiology, Mie University School of Medicine, Edobashi 2-174, Tsu, Mie 5148507, Japan, JP |
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Abstract: | The mechanism of airway remodeling in asthmatic patients is poorly understood. Thrombin is a multifunctional protease that,
in addition to its critical role in thrombotic processes, has also been described as inducing cellular and molecular events
relevant to tissue remodeling. The present investigation was undertaken to evaluate the activity of thrombin in the sputum
of asthmatic patients and its potential role in airway remodeling. The study population comprised 8 healthy subjects and 14
stable patients with bronchial asthma. The concentrations of thrombin, thrombin-antithrombin complex (TAT), and tissue factor
were measured in the sputum of all subjects. The concentrations of thrombin (p= 0.007), TAT (p= 0.01), and tissue factor (p= 0.02) in sputum were significantly higher in asthmatic patients than in healthy controls. The proliferative effects that
sputum from asthmatic patients (p= 0.01) and thrombin (p= 0.03) have on cultured human smooth muscle cells was inhibited significantly in the presence of recombinant hirudin, a specific
thrombin inhibitor. Significant statistical correlation was observed between the degree of bronchial responsiveness and the
sputum concentrations of thrombin (r=−0.8; p= 0.02) and TAT (r=−0.9; p= 0.01). The results of this study showed that increased thrombin generation occurs in the airway of patients with asthma
and that it may play a role in the pathogenesis of airway remodeling. Further studies should be carried out to assess whether
these findings are also observed in other airway diseases.
Accepted for publication: 6 April 1999 |
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Keywords: | : Thrombin— Asthma— Remodeling— Smooth muscle cell |
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