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- W4313306025 startingPage "2293" @default.
- W4313306025 abstract "Abstract We report the results and analysis of dose-response and desensitization studies of rabbit basophils by a variety of antigens. Unlike the response of human basophils, the histamine release curves rarely rise and fall in a symmetric fashion, but more often either rise to a plateau, peak, and then fall to a non-zero plateau, or exhibit bimodality. In those cases in which the curves peak, preincubation with antigen in the absence of Ca++ has a smaller effect at the high and low concentration portions of the curve than it does toward the center, where the inhibitory effect is maximum. We show that the results can be explained by a simple model in which: 1) The signals for release and desensitization both increase as the concentration of receptor cross-links increases and 2) the signals reach a plateau (i.e., they have a maximum value) when the number of receptor cross-links becomes sufficiently large. By changing the parameters of the model, the balance between desensitization and release changes, and all the observed patterns can be reproduced. In particular, if both signals saturate (reach their maximum value) at a ligand concentration below that of maximum cross-linking, the histamine release curve will plateau. If the release signal saturates but the inhibitory signal continues to increase as ligand concentration increases toward its optimum value, the histamine release curve will be bimodal. Many of the parameters can be identified with those that affect receptor clustering. These include the affinity of IgE for the antigen, the number of IgE molecules per basophil, IgE hinge flexibility, membrane fluidity, and antigen concentration and valence. This identification permits a variety of additional predictions. One such prediction is that the difference between a dose-response curve that plateaus and one that is biphasic and unimodal reflects easier desensitization of cells responsible for the latter curve and/or that have a smaller number of cross-links. Both predictions are readily testable experimentally." @default.
- W4313306025 created "2023-01-06" @default.
- W4313306025 creator A5027378666 @default.
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- W4313306025 date "1979-06-01" @default.
- W4313306025 modified "2023-09-25" @default.
- W4313306025 title "Receptor Cross-Linking and Histamine Release" @default.
- W4313306025 doi "https://doi.org/10.4049/jimmunol.122.6.2293" @default.
- W4313306025 hasPublicationYear "1979" @default.
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