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)E-4, the prostaglandin (PG)D-2 metabolite and the mast cell marker 9alpha,11beta-PGF(2) 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-PGF(2) (91.9+/-8.2 versus 66.9+/-6.6 ng(.)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-PGF(2) (68.4+/-6.9 versus 56.0+/-5.8 ng(.)mmol creatinine(-1)) and LTE4 (58.5+/-5.3 versus 43.0+/-3.3 ng(.)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 F-2 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.