Nonspecific desensitization, functional memory, and the characteristics of SHIP phosphorylation following IgE-mediated stimulation of human basophils
Nonspecific desensitization, functional memory, and the characteristics of SHIP phosphorylation following IgE-mediated stimulation of human basophils
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DOI：
10.4049/jimmunol.177.2.1040
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发表时间：
2006-07-15
影响因子：
4.4
通讯作者：
Vilarino, Natalia
中科院分区：
文献类型：
--
作者：
MacGlashan, Donald, Jr.;Vilarino, Natalia
先前对嗜碱性粒细胞分泌的研究已经证明了称为非特异性脱敏的现象，一种IgE介导的刺激改变细胞对其他非交叉反应IgE介导的刺激的反应的能力，并且推测改变磷脂酰肌醇3，4，5-磷酸水平的过程是非特异性脱敏的原因。目前的研究检查了SHIN磷酸化的变化和特征，作为SHIP 1参与反应的量度。根据早期的研究，有两个预测没有被观察到。首先，SHIP 1磷酸化的动力学与其他早期信号的反应动力学相似，并恢复到静息水平，而非特异性脱敏仍然存在。其次，与预期的过度SHIP磷酸化相反，处于非特异性脱敏状态的细胞显示出减少的SHIP磷酸化（与先前未暴露于非交叉反应性Ag的细胞相比）。不一致的预期，从非特异性脱敏，治疗细胞与DNP-赖氨酸解离结合DNP-HSA，增强或没有影响SHIP磷酸化后的第二个Ag。这些实验还显示了一种脱敏形式，尽管脱敏银解离，但这种脱敏形式仍持续存在。最近的研究和这些研究的结果表明，早期信号成分如syk激酶的丢失可能是非特异性脱敏的一些影响，并导致对先前刺激的免疫记忆的形式。总之，SHIP磷酸化的各种特征与参与非特异性脱敏的信号传导元件的预期不一致，而是本身经历非特异性脱敏的信号传导元件。
Previous studies of secretion from basophls have demonstrated the phenomenon called nonspecific desensitization, the ability of one IgE-mediated stimulus to alter the cell's response to other non-cross-reacting IgE-mediated stimuli, and a process that would modify phosphatidylinositol 3,4,5-phosphate levels was speculated to be responsible for nonspecific desensitization. The current studies examined the changes and characteristics of SHIN phosphorylation as a measure of SHIP1 participation in the reaction. Based on the earlier studies, two predictions were made that were not observed. First, the kinetics of SHIP1 phospborylation were similar to reaction kinetics of other early signals and returned to resting levels while nonspecific desensitization remained. Second, in contrast to an expected exaggerated SHIP phosphorylation, cells in a state of nonspecific desensitization showed reduced SHIP phosphorylation (compared with cells not previously exposed to a non-cross-reacting Ag). Discordant with expectations concerning partial recovery from nonspecific desensitization, treatment of cells with DNP-lysine to dissociate bound DNP-HSA, either enhanced or had no effect on SHIP phosphorylation following a second Ag. These experiments also showed a form of desensitization that persisted despite dissociation of the desensitizing Ag. Recent studies and the results of these studies suggest that loss of early signaling components like syk kinase may account for some of the effects of nonspecific desensitization and result in a form of immunological memory of prior stimulation. Taken together, the various characteristics of SHIP phosphorylation were not consistent with expectations for a signaling element involved in nonspecific desensitization, but instead one which itself undergoes nonspecific desensitization.