Mast cell tryptase potentiates histamine-induced contraction in human sensitized bronchus.
The mast cell plays a pivotal role in the early asthmatic response via release of mediators, which directly influence airway smooth muscle tone. Canine mast cell tryptase has been reported to potentiate the contractile response of canine isolated airways to histamine. The aim of this study was to investigate whether human mast cell tryptase potentiated contractile responses in human isolated bronchi. The effect of tryptase differed according to the sensitization status of the bronchi. In lung tissue from sensitized patients (those whose bronchial tissue contracted in response to the application of any of four common antigens) 90 ng.mL-1 of human purified lung tryptase markedly potentiated the contractile response to histamine. The maximal response as a percentage of maximal contraction to acetylcholine was 80 +/- 8% in control tissues and 119 +/- 6% in tryptase treated tissues (n = 4; p < 0.05). Tryptase, at a dose of 200 ng.mL-1, also potentiated responses but to a lesser degree, 100 +/- 5% (n = 4; p < 0.05). In nonsensitized bronchi, neither 90 nor 200 ng.mL-1 tryptase had any significant effect on histamine responses. The increased response in the presence of tryptase in sensitized tissue was inhibited by the calcium voltage-dependent channel antagonist, verapamil (10(-6) M). We have shown, for the first time, that human mast cell tryptase potentiates contraction in sensitized bronchi via a calcium-related mechanism. These findings provide a link between a mast cell derived product and in vitro human airway hyperresponsiveness.
Johnson
P R
PR
Dept of Pharmacology, University of Sydney NSW, Australia.
Ammit
A J
AJ
Carlin
S M
SM
Armour
C L
CL
Caughey
G H
GH
Black
J L
JL
D000109:Acetylcholine / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000503:physiopathology; D001980:Bronchi / Q000187:drug effects*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D053818:Chymases; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000201:enzymology* / Q000502:physiology; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D012697:Serine Endopeptidases / Q000008:administration & dosage / Q000494:pharmacology*; D053802:Tryptases; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D018836:Inflammation Mediators; D006632:Histamine; D014700:Verapamil; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases; D000109:Acetylcholine