| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2542644 | International Immunopharmacology | 2007 | 9 Pages |
Mast cell stimulation leads to an early response with histamine release and prostaglandin (PGD2) production but attempts to link these two events have been contradictory. In IgE-mediated mast cell activation, a late-phase PGD2-production is caused by increased cyclooxygenase-2 (COX-2) expression whereas a COX-2 involvement in the early response is uncertain. The present study compares the influence of four COX-inhibitors (NSAIDs) on the histamine release of mast cells from naïve and actively sensitized rats. NSAIDs of different COX-1 vs. COX-2 selectivity were used, i.e. acetylsalicylic acid (ASA), piroxicam, meloxicam, and NS-398, a selective COX-2-inhibitor. All could inhibit antigen-induced histamine release, with 64%, 34%, 27% and 85% inhibition by ASA (5 mM), piroxicam (100 μM), meloxicam (100 μM) and NS-398 (100 μM), respectively. Similar inhibition was found with compound 48/80 without calcium added to the medium whereas compound 48/80 with calcium was affected less by ASA and NS-398 and unaffected by the oxicams. Only small differences between the two kinds of mast cells were found, except with NS-398 which was a significantly more effective inhibitor of naïve than sensitized cells when exposed to compound 48/80 with calcium present. The results do not show any consistent relationship between the influence of the NSAIDs and their COX-2-selectivity. The high NSAID-concentrations required for inhibition cast doubt about an involvement of COX-inhibition and indicate additional or other targets. The results seem to exclude toxic effects on mast cell energy production but are consistent with an interference with the calcium disposition.
