PMID- 19302592
OWN - NLM
STAT- MEDLINE
DCOM- 20100105
LR  - 20211020
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 156
IP  - 8
DP  - 2009 Apr
TI  - Inhibition of anti-IgE mediated human mast cell activation by NO donors is 
      dependent on their NO release kinetics.
PG  - 1279-86
LID - 10.1111/j.1476-5381.2009.00120.x [doi]
AB  - 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. 
      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. 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. 
      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.
FAU - Yip, K H
AU  - Yip KH
AD  - Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong 
      Kong, Hong Kong SAR, China.
FAU - Leung, F P
AU  - Leung FP
FAU - Huang, Y
AU  - Huang Y
FAU - Lau, H Y A
AU  - Lau HY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090319
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (1-hexanamine-6-(2-hydroxy-1-methyl-2-nitrosohydrazine)-N-methyl)
RN  - 0 (Anti-Allergic Agents)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antibodies)
RN  - 0 (Antioxidants)
RN  - 0 (Benzoates)
RN  - 0 (Hydrazines)
RN  - 0 (Imidazoles)
RN  - 0 (Nitric Oxide Donors)
RN  - 145757-47-7 
      (1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole)
RN  - 169D1260KM (Nitroprusside)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 79032-48-7 (S-Nitroso-N-Acetylpenicillamine)
RN  - 86831-65-4 (1,1-diethyl-2-hydroxy-2-nitrosohydrazine)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Anti-Allergic Agents/metabolism/*pharmacology
MH  - Anti-Inflammatory Agents/metabolism/*pharmacology
MH  - Antibodies
MH  - Antioxidants/pharmacology
MH  - Benzoates/pharmacology
MH  - Cell Degranulation/*drug effects
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Histamine Release/*drug effects
MH  - Humans
MH  - Hydrazines/metabolism/pharmacology
MH  - Imidazoles/pharmacology
MH  - Immunoglobulin E/*immunology
MH  - Kinetics
MH  - Mast Cells/*drug effects/immunology/metabolism
MH  - Nitric Oxide/*metabolism
MH  - Nitric Oxide Donors/metabolism/*pharmacology
MH  - Nitroprusside/metabolism/pharmacology
MH  - S-Nitroso-N-Acetylpenicillamine/metabolism/pharmacology
MH  - Superoxide Dismutase/metabolism
PMC - PMC2697744
EDAT- 2009/03/24 09:00
MHDA- 2010/01/06 06:00
PMCR- 2010/04/01
CRDT- 2009/03/24 09:00
PHST- 2009/03/24 09:00 [entrez]
PHST- 2009/03/24 09:00 [pubmed]
PHST- 2010/01/06 06:00 [medline]
PHST- 2010/04/01 00:00 [pmc-release]
AID - BPH120 [pii]
AID - 10.1111/j.1476-5381.2009.00120.x [doi]
PST - ppublish
SO  - Br J Pharmacol. 2009 Apr;156(8):1279-86. doi: 10.1111/j.1476-5381.2009.00120.x. 
      Epub 2009 Mar 19.