Comparison of the Modulatory Effect of Ketotifen, Sodium Cromoglycate, Procaterol and Salbutamol in Human Skin, Lung and Tonsil Mast Cells

Abstract

To assess the influence of mast cell heterogeneity on the inhibition of mediator release by drugs, the effects of ketotifen, sodium cromoglycate and β-adrenoceptor agonists were examined against IgE-dependent histamine and prostaglandin D₂ release from enzymatically dispersed human skin, lung and tonsil-lar mast cells. At high concentrations, ketotifen was an inhibitor of histamine and prostaglandin D₂ release from lung and tonsillar mast cells. No cross-tachyphylaxis with sodium cromoglycate was seen. In skin mast cells no inhibition of mediator release was observed with 1.0 μM ketotifen, above which histamine release was induced. Sodium cromoglycate was a weak inhibitor of histamine and prostaglandin D₂ release from lung and tonsillar mast cells and showed tachyphylaxis. Sodium cromoglycate did not inhibit histamine and prostaglandin D₂ release from skin mast cells. On the other hand, no heterogeneity was observed with the β-adrenoceptor agonists, procaterol and salbutamol. β-Adrenoceptor stimulants were significantly more effective in inhibiting prostaglandin D₂ than histamine release. No tachyphylaxis was seen with prolongation of the incubation time before challenge. Our results suggest that human mast cells are heterogeneous with respect to the modulation of mediator release by ketotifen and sodium cromoglycate but not β-adrenoceptor agonists.

T Cell Proliferation by Direct Cross-Talk between OX40 Ligand on Human Mast Cells and OX40 on Human T Cells: Comparison of Gene Expression Profiles between Human Tonsillar and Lung-Cultured Mast Cells

“…Tonsillar MCs were enzymatically dispersed as described previously (27)(28)(29). The dispersed cells were resuspended by IMDM (Invitrogen Life Technologies, Grand Island, NY) containing 3 g/ml fungizone (Invitrogen Life Technologies) and 100 U/ml penicillin-streptomycin (Invitrogen Life Technologies).…”

Differential Effects of .BETA.2-Adrenoceptor Desensitization on the IgE-Dependent Release of Chemical Mediators from Cultured Human Mast Cells

“…6,8,13,14) Furthermore, b 2 -adrenoceptor agonists inhibit PGD 2 and LT release more potently than histamine release from human mast cells. 11,13,14) On the other hand, desensitization has also been observed in the inhibition of human mast cell histamine release by b 2 -adrenoceptor agonists. [17][18][19] Chong and Peachell 18) reported that isoproterenol inhibition of histamine release from human lung mast cells is considerably more susceptible to desensitizing treatments than the isoproterenol relaxation of bronchial smooth muscle.…”

“…4,5) It has been reported that b 2 -adrenoceptor agonists inhibit IgE-mediated release of mediators such as histamine, prostaglandin D 2 (PGD 2 ), and cysteinyl leukotrienes (LT) from human lung fragments, [6][7][8][9] and dispersed human lung and skin mast cells. [10][11][12][13] We also reported that b 2 -adrenoceptor agonists inhibit the chemical mediator release in cultured human mast cells.14-16) b 2 -Adrenoceptor agonists inhibit mediator release from human mast cells far more potently than disodium cromoglycate. 6,8,13,14) Furthermore, b 2 -adrenoceptor agonists inhibit PGD 2 and LT release more potently than histamine release from human mast cells.…”

“…[10][11][12][13] We also reported that b 2 -adrenoceptor agonists inhibit the chemical mediator release in cultured human mast cells.…”

Anti‐inflammatory effects of theophylline, cromolyn and salbutamol in a murine model of pleurisy

“…Moreover, the lung anti-inflammatory properties of cromolyn have also been reviewed (for review see: Barnes, 1989; Bernstein & Bernstein, 1993). Thus, besides its potent anti-allergic effect which inhibits the release of anaphylactic mediators from mast cells (Tainsh et al, 1991;Okayama & Church, 1992), another proposed mechanism of action of cromolyn is its ability to inhibit neural reflex bronchoconstriction induced by several neuropeptides that take part in the neurogenic inflammatory process (Morley, 1994). This would result in a marked inhibition of the inflammatory cells and consequently of the release of several mediators which, in turn, would attenuate their spasmogenic effects on smooth muscle tone (Bernstein & Bernstein, 1993).…”