Evidence of mast cell activation and leukotriene release after mannitol inhalation.
The aim of this study was to investigate if mannitol inhalation, as a model of exercise-induced bronchoconstriction (EIB), causes mast cell activation and release of mediators of bronchoconstriction. Urinary excretion of previously identified mediators of EIB was investigated in association with mannitol-induced bronchoconstriction. Twelve asthmatic and nine nonasthmatic subjects inhaled mannitol and urine was collected 60 min before and for 90 min after challenge. The urinary concentrations of leukotriene (LT)E4, the prostaglandin (PG)D2 metabolite and the mast cell marker 9alpha,11beta-PGF2 were measured by enzyme immunoassay. N(tau)-methylhistamine was measured by radioimmunoassay. In asthmatic subjects, inhalation of a mean+/-SEM dose of 272+/-56 mg mannitol induced a reduction in forced expiratory volume in one second (FEV1) of 34.5+/-2.1%. This was associated with increases in urinary 9alpha,11beta-PGF2 (91.9+/-8.2 versus 66.9+/-6.6 ng x mmol creatinine(-1), peak versus baseline) and LTE4 (51.3+/-7.5 versus 32.9+/-4.7). In nonasthmatic subjects, the reduction in FEV1 was 1.0+/-0.5% after inhaling 635 mg of mannitol. Although smaller than in the asthmatics, significant increases of urinary 9alpha,11beta-PGF2 (68.4+/-6.9 versus 56.0+/-5.8 ng x mmol creatinine(-1)) and LTE4 (58.5+/-5.3 versus 43.0+/-3.3 ng x mmol creatinine(-1)) were observed in the nonasthmatic subjects. There was also a small increase in urinary excretion of N(tau)-methylhistamine in the nonasthmatics, but not in the asthmatics. The increased urinary levels of 9alpha,11beta-prostaglandin F2 support mast cell activation with release of mediators following inhalation of mannitol. Increased bronchial responsiveness to the released mediators could explain the exclusive bronchoconstriction in asthmatic subjects.
D000328:Adult; D001249:Asthma / Q000175:diagnosis / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000502:physiology*; D016022:Case-Control Studies; D015237:Dinoprost / Q000652:urine; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007124:Immunoenzyme Techniques; D017999:Leukotriene E4 / Q000652:urine; D015289:Leukotrienes / Q000378:metabolism* / Q000652:urine; D008297:Male; D008353:Mannitol; D008407:Mast Cells / Q000276:immunology*
D015289:Leukotrienes; D008353:Mannitol; D017999:Leukotriene E4; D015237:Dinoprost