Degranulation of human basophils: quantitative analysis of histamine release and desensitization, due to a bivalent penicilloyl hapten.
Degranulation of human basophils: quantitative analysis of histamine release and desensitization, due to a bivalent penicilloyl hapten.
复制标题
人嗜碱性粒细胞脱颗粒：二价青霉酰半抗原导致的组胺释放和脱敏的定量分析。
DOI：
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发表时间：
1979
影响因子：
4.4
通讯作者：
L. Lichtenstein
中科院分区：
文献类型：
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作者：
M. Dembo;B. Goldstein;A. Sobotka;L. Lichtenstein
我们提出了由于对称二价半抗原双苯甲基青酰基 1,6 二氨基己烷 (BPO)2 从人类嗜碱性粒细胞中释放组胺的定量模型。模型的主要要素是：1）嗜碱性粒细胞的组胺含量被划分为大量离散且准独立的“量子”。 2) 嗜碱性粒细胞群体中的一定比例的量子是不可释放的。 3) 量子内容的释放是一个随机事件。 4)(BPO)2和细胞表面IgE之间的结合和交联反应在与嗜碱性粒细胞释放组胺或脱敏的时间尺度相比非常短的时间尺度上接近热平衡。 5) 每单位时间释放事件的概率 PR 是细胞外钙浓度 [Ca]ex 和每个细胞交联 IgE 分子数量 Xpoly 的函数。此外，对于固定的[Ca]ex，PR 对Xpoly 的函数依赖性是S 形的，并且PR 对[Ca]ex 的依赖性是这样的：对于Xpoly 的所有值，PR → 0 作为[Ca]ex → 0。 6) 抗原特异性IgE分子和/或其相关Fc受体以Xpoly可饱和函数的速率失活。此外，这种失活过程不依赖于细胞外钙浓度。
通过对使用来自单个供体的细胞获得的组胺释放数据进行详细拟合来测试该模型。理论与实验得到了很好的吻合，并确定了模型的所有参数。简要讨论了将该模型扩展到包括比 (BPO)2 系统更复杂的系统的方法。
We present a quantitative model of histamine release from human basophils due to the symmetric bivalent hapten, Bis benzylpencilloyl 1,6 diaminohexane, (BPO)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)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 basophils. 5) The probability per unit time of the release event, PR, is a function of the extracellular calcium concentration [Ca]ex, and of the number of cross-linked IgE molecules per cell, Xpoly. In addition, the functional dependence of PR on Xpoly for fixed [Ca]ex is sigmoid, and the dependence of PR on [Ca]ex is such that PR → 0 as [Ca]ex → 0 for all values of Xpoly. 6) Antigen-specific IgE molecules and/or their associated Fc receptors are inactivated at a rate that is a saturable function of Xpoly. 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 model are determined. The ways in which the model can be extended to include systems more complex than the (BPO)2 system are briefly discussed.