A sequence of biochemical events in the antigen-induced release of chemical mediators from sensitized human lung tissue

Five sequential steps interspaced between the antigen activation of human lung fragments sensitized with IgE and the release of the chemical mediators, histamine and slow-reacting substance of anaphylaxis (SRS-A), have been delineated. The experimental design that permits this analysis is based upon the capacity to maintain the serine esterase essential to mediator release in its diisopropylphosphofluoridate (DFP)-resistant precursor state despite antigen challenge and upon the ability to arrest reversibly the reaction sequence by various manipulations. When sensitized lung fragments are challenged with antigen in the presence of DFP, a serine esterase is converted to its active DFP-inhibitable state; this conversion is prevented if antigen challenge in the presence of DFP occurs in calcium-free buffer indicating that immunologic activation of the esterase requires extracellular calcium. The fact that calcium depletion alone does not impair antigen-induced histamine release implies that prevention of esterase activation depends upon both the absence of extracellular calcium and the inactivation of any active esterase by DFP to prevent an autocatalytic feedback activation. Arresting the antigen-induced activation of the serine e...Continue Reading