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Inhibition of anti-IgE mediated human mast cell activation by NO donors is dependent on their NO release kinetics.
- Source :
-
British journal of pharmacology [Br J Pharmacol] 2009 Apr; Vol. 156 (8), pp. 1279-86. Date of Electronic Publication: 2009 Mar 19. - Publication Year :
- 2009
-
Abstract
- Background and Purpose: Although the mast cell is a source of nitric oxide (NO), the effect of NO on human mast cells has not been defined. This study investigated if exogenous NO could affect human mast cell activation.<br />Experimental Approach: Effects of different NO donors on immunoglobulin E (IgE)-dependent activation of human-cultured mast cells (HCMC) derived from precursors in buffy coat were investigated by measuring histamine release. Intracellular NO in HCMC was monitored with confocal microscopy using the fluorescent NO indicator 4-amino-5-methylamino-2', 7'-difluorofluorescein.<br />Key Results: Diethylamine NONOate (DEA/NO) and MAHMA NONOate (NOC-9), both have rapid NO release rates, only inhibited anti-IgE-induced histamine release when added to HCMC at the time of activation. NO donors with slower NO release kinetics were ineffective even after 30 min incubation. Confocal microscopy revealed that the effectiveness of NO donors was dependent on the availability of adequate NO inside HCMC during activation. The inhibitory action of DEA/NO was diminished by the NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl but potentiated by the anti-oxidant, N-acetylcysteine (NAC). Furthermore, co-incubation with NAC allowed previously ineffective NO donors to suppress HCMC activation and thus suggested that NAC could increase the availability of NO from NO donors.<br />Conclusions and Implications: Our results demonstrated that NO was able to modulate human mast cell activation but only when enough NO was present at the time of cell activation. Our findings explain the controversy over the effectiveness of NO on mast cell degranulation and supports the possibility that NO donors could be beneficial for treating allergic inflammation.
- Subjects :
- Acetylcysteine pharmacology
Anti-Allergic Agents metabolism
Anti-Inflammatory Agents metabolism
Antibodies
Antioxidants pharmacology
Benzoates pharmacology
Cells, Cultured
Dose-Response Relationship, Drug
Humans
Hydrazines metabolism
Hydrazines pharmacology
Imidazoles pharmacology
Kinetics
Mast Cells immunology
Mast Cells metabolism
Nitric Oxide Donors metabolism
Nitroprusside metabolism
Nitroprusside pharmacology
S-Nitroso-N-Acetylpenicillamine metabolism
S-Nitroso-N-Acetylpenicillamine pharmacology
Superoxide Dismutase metabolism
Anti-Allergic Agents pharmacology
Anti-Inflammatory Agents pharmacology
Cell Degranulation drug effects
Histamine Release drug effects
Immunoglobulin E immunology
Mast Cells drug effects
Nitric Oxide metabolism
Nitric Oxide Donors pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5381
- Volume :
- 156
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- British journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 19302592
- Full Text :
- https://doi.org/10.1111/j.1476-5381.2009.00120.x