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Histamine Release: In Vitro Studies of the Inhibitory Region of the Dose-Response Curve¹

From the Department of Medical Immunology, The Public Health Research Institute of the City of New York, Inc., New York, New York 10016

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.

Footnotes

¹ This work was supported in part by Grant GB31738X from the National Science Foundation, IC-391 from the American Cancer Society, Inc., and AI-08710 from the United States Public Health Service.

² Recipient of Post-Doctoral Fellowship Training Grant AI-408-02 from the National Institute of Allergy and Infectious Diseases.

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