Dembo M, Goldstein B
Cell. 1980 Nov;22(1 Pt 1):59-67. doi: 10.1016/0092-8674(80)90154-3.
We present a model for the control of immunoglobulin E (IgE)-mediated histamine release from human basophils. We suggest that there is a calcium gating factor which interacts with crosslinked IgE to form a short-lived open calcium channel. After formation of the channel the activated gating factor rapidly decays to an inactive form. It is the loss of the active gating factor which causes the basophil to desensitize nonspecifically. We propose that the crosslinked IgE molecules are deactivated by a mechanism, such as endocytosis or shedding, which is independent of the mechanism which inactivates the calcium gating factor. This loss of functional IgE leads to specific desensitization. The mathematical formulation of the model explains the relationship of specific and nonspecific desensitization to the amount of specific IgE on the basophil surface; explains why there are two types of antigen excess inhibition; explains the relationship between antigen excess inhibition and desensitization; explains why, for a fixed antigen concentration, increasing the concentration of cell surface IgE increases histamine release until an optimal concentration is reached, then decreases histamine release; predicts the effects that changing the external calcium will have on the dose response curve; and predicts that increasing the amount of specific IgE on the cell surface will cause the dose response curve to undergo a transition from a curve with a single maximum to a curve with two maxima.
我们提出了一种用于控制免疫球蛋白E（IgE）介导的人嗜碱性粒细胞组胺释放的模型。我们认为存在一种钙门控因子，它与交联的IgE相互作用形成一个短暂开放的钙通道。通道形成后，活化的门控因子迅速衰变为无活性形式。正是活性门控因子的丧失导致嗜碱性粒细胞发生非特异性脱敏。我们提出交联的IgE分子通过一种机制失活，如内吞作用或脱落，这种机制独立于使钙门控因子失活的机制。功能性IgE的这种丧失导致特异性脱敏。该模型的数学公式解释了特异性和非特异性脱敏与嗜碱性粒细胞表面特异性IgE量之间的关系；解释了为什么存在两种类型的抗原过量抑制；解释了抗原过量抑制与脱敏之间的关系；解释了为什么对于固定的抗原浓度，增加细胞表面IgE的浓度会增加组胺释放，直到达到最佳浓度，然后组胺释放减少；预测了改变外部钙对剂量反应曲线的影响；并预测增加细胞表面特异性IgE的量将导致剂量反应曲线从具有单个最大值的曲线转变为具有两个最大值的曲线。
