Tryptase mediates hyperresponsiveness in isolated Guinea Pig bronchi

Hyperresponsiveness of airway smooth muscle to allergens and environmental factors has long been associated with the pathophysiology of asthma. Tryptase, a serine protease of lung mast cells, has been implicated as one of the mediators involved in the induction of hyperresponsiveness. As a consequen...

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Bibliographic Details
Published in:Life sciences (1973) 1998, Vol.63 (26), p.2295-2303
Main Authors: Barrios, Victor E., Middleton, Scot C., Kashem, Mohammed A., Havill, Andy M., Toombs, Christopher F., Wright, Clifford D.
Format: Article
Language:English
Subjects:
Animals
Bronchial Hyperreactivity - etiology
Chymases
Dipeptides - pharmacology
Dose-Response Relationship, Drug
Guinea Pigs
Histamine - pharmacology
Humans
hyperresponsiveness
In Vitro Techniques
Male
Proteinase Inhibitory Proteins, Secretory
Proteins - pharmacology
Secretory Leukocyte Peptidase Inhibitor
Serine Endopeptidases - physiology
SLPI
tryptase
Tryptases
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Summary:Hyperresponsiveness of airway smooth muscle to allergens and environmental factors has long been associated with the pathophysiology of asthma. Tryptase, a serine protease of lung mast cells, has been implicated as one of the mediators involved in the induction of hyperresponsiveness. As a consequence, tryptase inhibitors have become the subject of study as potential novel therapeutic agents for asthma. Secretory leukocyte protease inhibitor (SLPI) is a naturally occurring protein of human airways which exhibits anti-tryptase activity. To assess the potential therapeutic utility of SLPI in asthma, its effects were evaluated using in vitro and ex vivo models of airway hyperresponsiveness and compared with the effects of the small molecule tryptase inhibitor APC-366. Our results demonstrate that SLPI inhibits tryptase-mediated hyperresponsiveness in vitro and attenuates the hyperresponsiveness observed in airway smooth muscle from antigen-sensitized animals subjected to antigen exposure. The small molecule tryptase inhibitor APC-366 has a similar inhibitory effect. Thus, tryptase appears to be a significant contributor to the development of hyperresponsiveness in these models. To the extent that tryptase contributes to the development and progression of asthma, SLPI may posses therapeutic potential in this disease setting.
ISSN:0024-3205
1879-0631
DOI:10.1016/S0024-3205(98)00518-9