Inhibition of mouse mast cell proliferation and proinflammatory mediator release by benzodiazepines.
Mast cell (MC) activation may occur in vitro and in vivo following stimulation with various immunologic or nonimmunologic agents. Such activation leads to the release of several biological mediators, including vasoactive amines, nitric oxide and cytokines, which account for the adverse effects observed during allergic reactions. While high affinity binding sites for benzodiazepines (BZDs) have been reported on MC, the effects of the ligation of these receptors on the proliferation of, and the mediator release from, these cells are poorly documented. In the present work, we have examined the effects of midazolam and of diazepam on the proliferation of mucosal (MMC)-like and of serosal (CTMC)-like mouse MC. In addition, we have studied the effects of these BZDs on beta-hexosaminidase, TNF-alpha and nitrite release induced from mouse mast cells through IgE receptor activation. We demonstrated that each of the two BZDs studied inhibited the proliferation of MMC- and CTMC-like elements in a dose-dependent fashion (10 to 100 microM). Furthermore, the BZDs inhibited the IgE-mediated release of beta-hexosaminidase, TNF-alpha and nitrites from MMC- or CTMC-like cells. Altogether, these data provide new insights into the pharmacological regulation of MC activation and may lead to the discovery of new and potent antiallergic compounds.
Bidri
M
M
Department of Cellular and Molecular Hematology, Faculty of Pharmacy, Paris, France.
Royer
B
B
Averlant
G
G
Bismuth
G
G
Guillosson
J J
JJ
Arock
M
M
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008874:Midazolam / Q000494:pharmacology; D009573:Nitrites / Q000378:metabolism; D010641:Phenotype; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D014151:Anti-Anxiety Agents; D018836:Inflammation Mediators; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D001619:beta-N-Acetylhexosaminidases; D003975:Diazepam; D008874:Midazolam