In vitro reversed anaphylaxis: characteristics of anti-IgE mediated histamine release.

Leucocytes from allergic and most normal human donors release histamine when challenged with antibodies against human γ-globulin. This reaction (reversed anaphylaxis) is due primarily to anti-IgE antibodies although there is some response in most donors to antisera against IgG even after it has been absorbed with light and ε chains. The anti-IgE is, however, several 100-fold more potent than the anti-IgG. By passive sensitization of the leucocytes of a normal donor with serum from a ragweed-allergic patient it was shown that the normal cells became sensitive to anti-IgE and ragweed antigen E at the same time; in both cases, there was an inverse relationship between the serum concentration used for passive sensitization and the concentration of antigen or antibody required for histamine release. There is a rough correlation ( = 0.42; <0.01) between the serum IgE concentration and the response of leucocytes from allergic donors to anti-IgE and an excellent correlation ( = 0.82; <0.01) between the response of the cells to ragweed antigen E and anti-IgE. There is also a strong parallel between the mechanism of direct, antigen mediated histamine release and the reversed reaction induced by anti-IgE. Both appear to be non-serum requiring, non-cytotoxic, secretory-like responses which are inhibited by theophylline, cyclic AMP and colchicine. These data suggest that cell bound IgE is of major importance in the anaphylactic response and that the direct and reversed anaphylactic reactions both operate through cell-bound IgE and share a common reaction mechanism.