Immunologic Release of Histamine and Slow Reacting Substance of Anaphylaxis from Human Lung

Abstract

Abstract The capacity of prostaglandins to suppress the IgE-dependent antigen-induced release of histamine from human lung tissue requires concentrations which increase tissue levels of cyclic adenosine 3′,5′-monophosphate (cyclic AMP) and involves a receptor distinct from that utilized by beta adrenergic agents. The inhibition of histamine release and concomitant rise of cyclic AMP in response to prostaglandin E1 (PGE1) occurs in a dose response fashion, reaching a peak within 1 min and persisting for at least 60 min. That the supression of mediator release from the subpopulation of target cells by the prostaglandins is related to elevations in total tissue cyclic AMP is supported by the kinetic relationship of the two events, the augmentation of both events in the presence of a methylxanthine, and the finding that the relative potency of isoproterenol, norepinephrine, PGE1 and prostaglandin F2α (PGF2α) to inhibit mediator release is in accord with their relative capacity to elevate cyclic AMP. The finding that low doses of prostaglandins enhance mediator release while reducing tissue levels of cyclic AMP reveals that these agents could profoundly modulate the immunologic release of chemical mediators.