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

Background Although the role of mediators and cytokines produced by mast ce lls is well established in asthmatic branchial inflammation, the contributi on of mast cell-derived proteases to the development of hyperresponsiveness remains unclear. There have been reports indicating that tryptase alters t he mechanical activity of animal airway smooth muscle or spontaneously sens itized 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 distrib ution of inflammatory cells i.e. immunohistochemistry. Results In both proximal and distal bronchi, the reactivity to histamine wa s significantly increased by a previous incubation in the presence of 1 mu g/mL of tryptase (increase in maximal force, Delta F-max was 12.1 +/- 3.8%, and 8.8 +/- 3.1%, respectively). This effect of tryptase on histamine-indu ced contraction was completely abrogated in the presence of the protease in hibitor benzamidine (100 mu mol/L). Histological examination of specimens e xposed to tryptase demonstrated an increase in mast cell number within the subepithelial tissue whereas mast cell numbers in the epithelial layer conc omittently 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.