Inhibition of IgE-dependent histamine release from human dispersed lung mast cells by anti-allergic drugs and salbutamol.
The ability of the anti-allergic drugs, sodium cromoglycate (SCG), lodoxamide, traxanox, RU31156 and the beta-adrenoceptor agonist salbutamol to inhibit IgE-dependent histamine and prostaglandin D2 (PGD2) release was assessed using human dispersed lung mast cells. The anti-allergic drugs were weak inhibitors of histamine release, high concentrations (100-1000 microM) producing less than 35% inhibition. Salbutamol produced 39% inhibition at 10 microM. The efficacy of both SCG and salbutamol was inversely related to the concentration of anti-IgE used for challenge and to the degree of histamine release. Rapid tachyphylaxis was observed with all anti-allergic drugs but not with salbutamol. Cross-tachyphylaxis was observed between SCG and the other anti-allergic drugs, suggesting a common mechanism of action. No cross-tachyphylaxis was observed between SCG and salbutamol. SCG was significantly (P less than 0.001) more effective in inhibiting PGD2 than it was histamine release. Preferential inhibition of PGD2 compared with histamine release was less marked (P less than 0.05) with salbutamol and not significant with the other anti-allergic drugs. Mast cells dispersed by enzymatic digestion of human lung released more histamine on immunological challenge than mechanically dispersed cells obtained by fine chopping of tissue. Enzyme treatment of mechanically dispersed cells removed this difference. Enzymatically and mechanically dispersed cells responded similarly to the inhibitory effects of SCG and salbutamol. Our results suggest that salbutamol is a more effective inhibitor of mediator release from human lung mast cells than anti-allergic drugs. However, with the low levels of mediator release achieved during an allergic reaction in man in vivo, both salbutamol and SCG are likely to be effective inhibitors of both preformed and newly generated mediators.
D000420:Albuterol / Q000494:pharmacology*; D004205:Cromolyn Sodium / Q000494:pharmacology; D003429:Cross Reactions / Q000187:drug effects; D006633:Histamine Antagonists / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D066298:In Vitro Techniques; D008168:Lung / Q000276:immunology; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015230:Prostaglandin D2; D011457:Prostaglandins D / Q000378:metabolism*
D006633:Histamine Antagonists; D011457:Prostaglandins D; D007073:Immunoglobulin E; D004205:Cromolyn Sodium; D000420:Albuterol; D015230:Prostaglandin D2