Release of prostaglandin D2 and leukotriene C4 in response to hyperosmolar stimulation of mast cells

Background: Mannitol-induced bronchoconstriction in subjects with exercise-induced asthma is associated with increased urinary excretion of 9 alpha, 11 beta-PGF(2), a metabolite of prostaglandin D-2 (PGD(2)) serving as a mast cell marker. It has however been questioned whether or not human mast cells release PGD(2) and leukotriene C-4 (LTC4) after osmotic challenge with mannitol in vitro. Methods: Cord blood-derived human mast cells were stimulated osmotically, immunologically or with a combination of both. Supernatants were analysed for PGD(2), LTC4 and histamine contents with enzyme immunoassays. Results: Significant release of de novo synthesized eicosanoids, predominantly PGD(2) [12 (8.8, 14) pmol/10(6)cells; median (25th, 75th percentile) but also LTC4 (0.1 (0.08, 0.15) pmol/10(6) cells] were found in mast cells in vitro in response to 0.7 M mannitol stimulation. A massive release of histamine [70 (5.3)% of total; mean (SEM)] was also found. There were no correlations between the levels of released mediators after mannitol stimulation. In contrast, there was a correlation between release of PGD(2) and LTC4, following immunological stimulation. Conclusion: The findings support that hyperosmolar challenge activates mast cells, but different than antigen stimulation.