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Degranulation of human basophils: quantitative analysis of histamine release and desensitization, due to a bivalent penicilloyl hapten

Journal Article · · J. Immunol.; (United States)
OSTI ID:5341333
We present a quantitative model of histamine release from human basophils due to the symmetric divalent hapten, Bis benzylpencilloyl 1,6 diaminohexane, (BPO)/sub 2/. The major elements of model are (1) The histamine content of basophils is divided into a large number of discrete and quasi-independent quanta. (2) A certain fraction of the quanta in a population of basophils are nonreleasable. (3) Release of the contents of a quanta is a stochastic event. (4) the binding and cross-linking reaction between (BPO)/sub 2/ and cell surface IgE approaches thermal equilibrium on a time scale that is very short compared to the time scale of histamine release from or desensitization of basephils. (5) The probability per unit time of the release event, P/sub R/, is a function of the extracellular calcium concentration (Ca)/sub ex/, and of the number of cross-linked IgE molecules per cell, X/sub poly/. In addition, the functional dependence of P/sub R/ on X/sub poly/ for fixed (Ca)sub ex/ is sigmoid, and the dependence of P/sub R/ on (Ca)/sub ex/ is such that P/sub R/ ..-->.. 0 as (Ca)/sub ex/ ..-->.. ( for all values of X/sub poly. (6) Antigen-specific IgE molecules and/or their associated Fe receptors are inactivated at a rate that is a saturable function of X/sub poly/. Furthermore, this process of inactivation is not dependent on the extracellular calcium concentration. The model is tested by carrying out a detailed fitting to histamine release data obtained by using cells from a single donor. Good agreement between theory and experiment is obtained, and all the parameters of the mode are determined. The ways in which the model can be extended to include systems more complex than the (BPO)/sub 2/ system are briefly discussed.
Research Organization:
Los Alamos Scientific Lab., NM
OSTI ID:
5341333
Journal Information:
J. Immunol.; (United States), Journal Name: J. Immunol.; (United States) Vol. 123:4; ISSN JOIMA
Country of Publication:
United States
Language:
English