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 9alpha, 11beta-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) (LTC(4)) 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), LTC(4) 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 LTC(4) (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 LTC(4), following immunological stimulation.


CONCLUSIONS
The findings support that hyperosmolar challenge activates mast cells, but different than antigen stimulation.
Gulliksson
M
M
Division of Physiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Palmberg
L
L
Nilsson
G
G
Ahlstedt
S
S
Kumlin
M
M
D002478:Cells, Cultured; D006801:Humans; D006982:Hypertonic Solutions; D007073:Immunoglobulin E / Q000502:physiology; D017997:Leukotriene C4 / Q000378:metabolism*; D008353:Mannitol / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000378:metabolism*
D006982:Hypertonic Solutions; D017997:Leukotriene C4; D007073:Immunoglobulin E; D008353:Mannitol; D015230:Prostaglandin D2