title: Effect of salbutamol, fenoterol, and sodium cromoglycate on the release of heparin from sensitized human lung fragments challenged with Dermatophagoides pteronyssinus allergen.
abstract: Heparin from degranulating mast cells influences a wide range of cellular and humoral reactions associated with allergic inflammation and asthma. Agents that inhibit mast cell degranulation may therefore compromise the moderating effects of heparin in the tissues and result in worsening inflammation and other associated pathology. This study measures heparin release from allergen-challenged human lung tissue and compares the effect of the mast cell stabilizing beta 2-agonists, salbutamol and fenoterol, and a non-beta 2-agonist, sodium cromoglycate, on the release of heparin. Pieces of lung tissue 2 to 3 mm3 were sensitized with high titer Dermatoaphagoides pteronyssinus-specific IgE serum and challenged with D. pteronyssinus allergen, with and without prior addition of salbutamol, fenoterol, or sodium cromoglycate. Dextran sulfate was added to the mixture to prevent the binding of heparin to tissue proteins. Heparin was released together with histamine after challenge. The mean and 95% confidence interval of prechallenge and postchallenge heparin concentrations in the lung tissue filtrates were 0.10 IU/ml (0.07, 0.12) and 0.24 IU/ml (0.17, 0.30), respectively (P < 0.001). Addition of the beta 2-agonists produced a mean inhibition of released heparin of 71% (50, 92), and 73% (55, 91), respectively. Sodium cromoglycate gave a 35% (20, 51) inhibition that was significantly less than that produced by the beta 2-agonists (P < 0.01). The beta 2-agonists salbutamol and fenoterol strongly inhibited heparin release from mast cells. The therapeutic use of mast cell stabilizing agents may therefore be potentially detrimental to the control of allergic inflammation and other associated pathologies.
authors.affiliation: Department of Medicine, University of Sydney, New South Wales, Australia.
authors.forename: W F
authors.initials: WF
authors.lastname: Green
authors.forename: K
authors.initials: K
authors.lastname: Konnaris
authors.forename: A J
authors.initials: AJ
authors.lastname: Woolcock
mesh_terms: D000420:Albuterol / Q000494:pharmacology*; D000485:Allergens / Q000276:immunology; D000818:Animals; D039741:Antigens, Dermatophagoides; D004205:Cromolyn Sodium / Q000494:pharmacology*; D016264:Dextran Sulfate; D005280:Fenoterol / Q000494:pharmacology*; D006493:Heparin / Q000378:metabolism*; D006494:Heparin Antagonists / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; D006494:Heparin Antagonists; D005280:Fenoterol; D006493:Heparin; D016264:Dextran Sulfate; D004205:Cromolyn Sodium; D000420:Albuterol