PMID- 9824389
OWN - NLM
STAT- MEDLINE
DCOM- 19990826
LR  - 20190831
IS  - 0954-7894 (Print)
IS  - 0954-7894 (Linking)
VI  - 28
IP  - 10
DP  - 1998 Oct
TI  - The effects of anti-asthma drugs on mediator release from cultured human mast 
      cells.
PG  - 1228-36
AB  - BACKGROUND: A method for generating human mast cells in vitro was recently 
      established. Little is known about the pharmacological profiles of allergic 
      mediator release from cultured mast cells. OBJECTIVE: The main objective was to 
      investigate the nature of cultured mast cells from a pharmacological point of 
      view. We examined the effect of anti-asthma drugs on the release of histamine, 
      sulfidoleukotrienes (LTs) and prostaglandin D2 (PGD2) from the cultured mast 
      cells. METHODS: Using the method established by Saito et al. we cultured cord 
      blood mononuclear cells in the presence of 80 ng/mL stem cell factor (SCF), 50 
      ng/mL interleukin-6 (IL-6) and 300 nmol/L prostaglandin E2 (PGE2), and obtained 
      almost pure (> 99%) mast cells. We sensitized cultured mast cells with 
      immunoglobulin E (IgE)-rich serum, and then treated them with some anti-asthma 
      drugs before challenge with anti-human IgE. Released histamine, LTs and PGD2 were 
      measured by high-performance liquid chromatography, commercial enzyme-linked 
      immunosorbent assay (ELISA) and enzyme immunoassay (EIA) systems, respectively. 
      RESULTS: The cultured mast cells released histamine, LTs and PGD2 following 
      immunological stimulation through IgE. The mast cell stabilizing agents disodium 
      cromoglycate (DSCG, 1 mmol/L) and azelastine (100 micromol/L) significantly 
      inhibited the release of these three mediators. The beta-adrenoceptor agonists 
      isoproterenol, salbutamol, and clenbuterol also inhibited all three mediators' 
      release in a concentration-dependent manner. The non-selective and selective 
      phosphodiesterase (PDE) inhibitors theophylline, rolipram, and cilostazol had no 
      significant effect on mediator release at clinically useful concentrations. BAY x 
      1005 (a 5-lipoxygenase-activating protein inhibitor) inhibited the LTs release, 
      whereas indomethacin (a cyclo-oxygenase I and II inhibitor) and NS-398 (a 
      cyclo-oxygenase II inhibitor) inhibited PGD2 release. CONCLUSIONS: The present 
      results indicate that cultured mast cells release histamine, LTs and PGD2 
      following IgE crosslinking. Anti-asthma drugs showed a characteristic suppression 
      of the release of each mediator. The suppressive actions of these drugs are 
      similar to their pharmacological actions on human lung mast cells. These results 
      suggest that cultured mast cells are useful for the analysis of function and 
      pharmacological profiles of lung mast cells.
FAU - Shichijo, M
AU  - Shichijo M
AD  - Department of Pharmacology, Gifu Pharmaceutical University, Gifu, Japan.
FAU - Inagaki, N
AU  - Inagaki N
FAU - Nakai, N
AU  - Nakai N
FAU - Kimata, M
AU  - Kimata M
FAU - Nakahata, T
AU  - Nakahata T
FAU - Serizawa, I
AU  - Serizawa I
FAU - Iikura, Y
AU  - Iikura Y
FAU - Saito, H
AU  - Saito H
FAU - Nagai, H
AU  - Nagai H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Exp Allergy
JT  - Clinical and experimental allergy : journal of the British Society for Allergy 
      and Clinical Immunology
JID - 8906443
RN  - 0 (Anti-Asthmatic Agents)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Leukotrienes)
RN  - RXY07S6CZ2 (Prostaglandin D2)
SB  - IM
CIN - Clin Exp Allergy. 1998 Oct;28(10):1171-3. PMID: 9824381
MH  - Anti-Asthmatic Agents/*pharmacology
MH  - Cells, Cultured
MH  - Chromatography, High Pressure Liquid
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Histamine Release/*drug effects
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Inflammation Mediators/*metabolism
MH  - Leukotrienes/metabolism
MH  - Mast Cells/*drug effects/metabolism
MH  - Prostaglandin D2/metabolism
EDAT- 1998/11/21 00:00
MHDA- 1998/11/21 00:01
CRDT- 1998/11/21 00:00
PHST- 1998/11/21 00:00 [pubmed]
PHST- 1998/11/21 00:01 [medline]
PHST- 1998/11/21 00:00 [entrez]
AID - 10.1046/j.1365-2222.1998.00394.x [doi]
PST - ppublish
SO  - Clin Exp Allergy. 1998 Oct;28(10):1228-36. doi: 10.1046/j.1365-2222.1998.00394.x.