IngentaConnect Mast cell tryptase as a mediator of hyperresponsiveness in human ...

Abstract:

Background

Although the role of mediators and cytokines produced by mast cells is well established in asthmatic bronchial inflammation, the contribution of mast cell-derived proteases to the development of hyperresponsiveness remains unclear. There have been reports indicating that tryptase alters the mechanical activity of animal airway smooth muscle or spontaneously sensitized human isolated airways. Objective

The aim of this study was to analyse the effect of purified mast cell tryptase on non-sensitized human isolated bronchi. Methods

Both central and peripheral bronchi, dissected from lung specimens obtained at thoracotomy, were studied in terms of both mechanical activity i.e. isometric contraction in response to a variety of agonists and distribution of inflammatory cells i.e. immunohistochemistry. Results

In both proximal and distal bronchi, the reactivity to histamine was significantly increased by a previous incubation in the presence of 1 μg/mL of tryptase (increase in maximal force, ΔF_max was 12.1 ± 3.8%, and 8.8 ± 3.1%, respectively). This effect of tryptase on histamine-induced contraction was completely abrogated in the presence of the protease inhibitor benzamidine (100 μmol/L). Histological examination of specimens exposed to tryptase demonstrated an increase in mast cell number within the subepithelial tissue whereas mast cell numbers in the epithelial layer concomittently decreased. Conclusion

These results indicate that human mast cell tryptase alters the contractile response of non-sensitized human isolated bronchi and that this alteration is accompanied by a change in the mast cell distribution within the airway wall.

Keywords: histamine; human bronchial smooth muscle; hyperresponsiveness; inflammation; mast cell tryptase; sensitization

Document Type: Research article

DOI: 10.1046/j.1365-2222.1999.00580.x

Affiliations: 1: Laboratoire de Physiologie Cellulaire Respiratoire (INSERM CRI 9806), Université Victor Segalen Bordeaux 2, Bordeaux, France, 2: Immunopharmacology Group, University of Southampton, UK

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Mast cell tryptase as a mediator of hyperresponsiveness in human isolated bronchi