Histamine Release: In Vitro Studies of the Inhibitory Region of the Dose-Response Curve

Abstract

Histamine release from the leukocytes of ragweed sensitive donors, which also release well to Fc-specific anti-IgE, was studied. In one type of experiment the effect of increasing concentrations of monomer anti-IgE (Fab) upon the release induced by anti-IgE was observed. for a suboptimum concentration of anti-IgE, increasing concentrations of the monomer inhibited the histamine release. However, for a supraoptimum concentration of anti-IgE, increasing concentrations of the monomer enhanced the histamine release. Evidence was also obtained which shows that supraoptimum concentrations of anti-IgE render the cells unresponsive to a near optimum concentration of antigen E. As the anti-IgE concentrations were increased into the inhibitory region the release due to antigen E was not maintained but dropped in parallel to the decrease due to the anti-IgE. High concentrations of monomer anti-IgE caused no inhibition of the antigen E induced release. The data imply, that for anti-IgE-induced release, the descending portion of the dose-response curve may be the result of a turn-off mechanism caused by an excess of bridging.