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The Immediate Allergic Response: in Vitro Separation of Antigen Activation, Decay and Histamine Release^1,2,

From the The Johns Hopkins University, School of Medicine, Baltimore, Maryland

Abstract

Antigen-induced, IgE-mediated histamine release can be separated into two stages: an antigen (or anti-IgE)-dependent, calcium-independent first stage, and an antigenindependent, calcium-dependent second stage. In the first stage at 37°C the cells are rapidly activated and, if the reaction proceeds longer than the optimal time (2 to 4 min), the activated state decays and leaves the cells unresponsive to further challenge by the homologous antigen or by a non-cross-reacting antigen. A 4°C first stage can also be generated which includes the antigen-antibody interaction but lacks a temperature sensitive chlorphenesin inhibitable step or steps. If separated from antigen after 2 to 4 min of the first stage, the activated cells are "stable" at 4°C for at least 30 min. The second or histamine release stage appears to begin immediately upon providing the activated cells with calcium. These experiments demonstrate the generation, by antigen, of an activity, presumably an enzyme or enzyme product, which is coupled to subsequent release stages by calcium; if uncoupled by calcium lack the enzyme/product is wasted and the cell becomes "desensitized." They also provide a number of cell intermediates for experimental manipulation.

Footnotes

¹ This study was supported by Research Grant AI 07290 from the National Institute of Allergy and Infectious Diseases.

² Portions of this work were presented at the meetings of the American Association of Immunologists and Collegium Internationale Allergologicum, and at the New York Academy of Sciences meeting on cyclic AMP.

³ Recipient of a Research Career Development Award from the National Institute of Allergy and Infectious Diseases.