Anti-inflammatory effect of β2-agonists: Inhibition of TNF-α release from human mast cells☆,☆☆,★,★★,♢
Section snippets
Materials
Collagenase from Clostridium histolyticum type I, hyaluronidase (type 1-s) from bovine testes, protease type XIV from Streptomyces griseus, N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid (HEPES), (±)-isoproterenol, (±)-propranolol (β1/β2 adrenergic receptor antagonist), and forskolin were purchased from Sigma Chemical Co. (St. Louis, Mo.). Isoproterenol, propranolol, and forskolin were dissolved in ascorbic acid (20 μg/ml), in water, in RPMI, and in 20 μl ethanol, respectively, and used
Effect of β2-agonists on histamine release from human skin mast cells
As a control for our studies on TNF-α release, we have compared the effect of salmeterol and isoproterenol on the release of histamine by human skin mast cells. Isolated and enriched human skin mast cells were sensitized with IgE, incubated with β2-agonists, salmeterol or isoproterenol, and stimulated with anti-human IgE antibody. The specific release of histamine from IgE-stimulated mast cells was 21% ± 3% (n = 14, the spontaneous release was always less than 5%). Treatment with isoproterenol
DISCUSSION
TNF-α is an important mediator of inflammatory responses.21 It plays a crucial role in the recruitment and stimulation of inflammatory cells.32 TNF-α is stored in mast cell granules20 and is actively synthesized and secreted by activated mast cells,33 macrophages,34 and other inflammatory cells.21 IgE-dependent activation increases the production of TNF-α by human lung and skin mast cells,28, 35 suggesting that TNF-α may have an important role in allergic reactions.
Although there was some
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Cited by (0)
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From the Department of Medicine, University of Alberta, Edmonton.
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Supported by Glaxo Group Research Ltd., U.K., and the Medical Research Council of Canada. E.Y.B. is a Scholar of the Medical Research Council/Canadian Lung Association; A.D.B. is a Scholar of the Alberta Heritage Foundation for Medical Research and the Astra Chair in Asthma Research.
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Reprint requests: Dr. Elyse Bissonnette, Pulmonary Research Group, Department of Medicine, HMRC 574, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.
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