IV. Immunologic mechanisms for release of chemical mediators of anaphylaxis from human lung tissue

The antigen-induced, IgE-dependent release of chemical mediators from human lung tissue in vitro is modulated by a variety of pharmacologic maneuvers involving alterations in the intracellular levels of cyclic nucleotides. Increase in the level of cyclic AMP inhibits the immunologic release of histamine, SRS-A and ECF-A; β-adrenergic agents, prostaglandins, cholera toxin and methylxanthines all produce accumulations of cAMP in human lung tissue. Depletion of cAMP after α-adrenergic, low-dose prostaglandin and imidazole stimulation is associated with enhancement of the release of mediators. Studies involving purified preparations of rat peritoneal mast cells confirm that alterations in the cAMP levels of a homogeneous population of target cells indeed influence histamine release in a fashion analogous to that of human lung tissue.Furthermore, cholinergic stimuli produce a marked enhancement of the antigen-induced release of mediators from human lung through an apparently independent mechanism, presumably acting through alterations in the tissue concentration of cyclic GMP. This latter observation suggests an important interaction between endogenously released parasympathetic neurohormones and the immunologic release of the chemical mediators of asthma.