Regulation of human skin mast cell histamine release by PDE inhibitors.
BACKGROUND
Mast cell and basophiles are thought to be central to inflammation that has an allergic basis as allergens activate these cells in an IgE-dependent manner to generate mediators such as histamine, eicosanoids and cytokines. Phosphodiesterase (PDE) is known to exist as multiple molecular forms of enzyme that metabolise the second messengers. Studies of our own have shown that, of a variety of isoform-selective drugs, the PDE4-selective inhibitors, such as rolipram, attenuate the IgE-mediated release of histamine from human basophiles but not from human lung mast cells (HLMC). The main aim of the present study was to characterise the type and role of PDEs regulating human skin mast cells by using selective and non-selective PDE inhibitors.


METHODS
Cells were pre-treated for 15 min with these agents and then challenged with an optimal releasing concentration of anti IgE (1:300) for a further 25 min for the release of histamine.


RESULTS
The data show that all the selective PDE-inhibitor compounds (10(-5)M) were ineffective whereas the non-selective PDE inhibitor, theophylline (10(-3)M), inhibited histamine release from HSMC (74 ± 4% inhibition; p<0.05). None of the selective PDE inhibitors had any effect on histamine release from HLMC whereas, in basophiles, compounds with activity at PDE 4 (rolipram, denbufylline, Ro-2017, Org 30029) were effective inhibitors of histamine release.


CONCLUSIONS
The data suggest that unlike most inflammatory cells, PDE-selective inhibitors are ineffective stabilisers of HSMC activity which is similar to HLMC.
Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Postal code: 81744-176, Isfahan, Iran. Electronic address: neskandari@med.mui.ac.ir.
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Eskandari
Department of Immunpharmacology, Faculty of Medicine, Karaj, Iran. Electronic address: rbastan@gmail.com.
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Bastan
Department of Immunology, Faculty of Medicine, Sheffield University of Medical Sciences, Yorkshire, UK. Electronic address: P.T.Peachell@sheffield.ac.uk.
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Peachell
D015550:Cell Degranulation; D002478:Cells, Cultured; D006632:Histamine / Q000378:metabolism*; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D008168:Lung / Q000473:pathology*; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology; D009930:Organic Chemicals / Q000494:pharmacology; D058988:Phosphodiesterase 4 Inhibitors / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D020889:Rolipram / Q000494:pharmacology; D012867:Skin / Q000473:pathology*; D013806:Theophylline / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D009930:Organic Chemicals; D058988:Phosphodiesterase 4 Inhibitors; D014970:Xanthines; C043898:denbufylline; C062763:ORG 30029; D007073:Immunoglobulin E; D006632:Histamine; D013806:Theophylline; D010727:Phosphoric Diester Hydrolases; D020889:Rolipram
Histamine; Mast cell; PDE