Relationship between spleen tyrosine kinase and phosphatidylinositol 5′ phosphatase expression and secretion from human basophils in the general population
Relationship between spleen tyrosine kinase and phosphatidylinositol 5′ phosphatase expression and secretion from human basophils in the general population
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DOI：
10.1016/j.jaci.2006.09.040
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发表时间：
2007-03-01
影响因子：
14.2
通讯作者：
MacGlashan, Donald W., Jr.
中科院分区：
文献类型：
--
作者：
MacGlashan, Donald W., Jr.
背景资料：以往的研究表明，脾酪氨酸激酶（syk）或磷脂酰肌醇5'磷酸酶（SHIP）的表达水平可以解释某些极端的人类嗜碱性粒细胞表型。目的：本研究旨在探讨在一般人群中syk和SHIP表达水平的变异性，单独或共同，是否可以解释嗜碱性粒细胞功能的变异性。对36名受试者的嗜碱性粒细胞进行了对IgE介导的刺激的最大反应性、敏感性和6种早期信号元件的表达水平的调查。在多元回归中，syk和SHIP一起可以解释67%的群体方差，尽管大部分方差是由syk表达解释的。表达量的变化规律为syk >> SHIP 1> SHIP 2接近林恩接近p85接近cbl，提示syk的表达主要受调控。已知IL-3调节syk水平，但我们发现与IL-3孵育3天导致其他信号传导元件的表达更大程度地增加：cbl > SHIEP 1> SHIP 2接近林恩接近p85 >= syk，与群体调查中的模式相反。与此相反，18小时的刺激，抗IgE抗体导致显着下调syk的表达，适度下调Fc是RI表达的一个元素，弱下调林恩的表达，并没有影响23其他signalingelements.Conclusion：与小鼠的研究不同，我们得出的结论是，表达syk是一个很好的预处理预测嗜碱性粒细胞的功能在一般人群。临床含义：syk水平的表达可能强烈影响嗜碱性粒细胞的功能反应，这一发现提示了特应性疾病严重程度的潜在机制。
Background: Previous studies have suggested that expression levels of spleen tyrosine kinase (syk) or phosphatidylinositol 5' phosphatase (SHIP) may explain certain extreme human basophil phenotypes.Objective: This study is designed to explore whether variability in syk and SHIP expression levels in the general population, alone or in concert, can account for the variability in basophil function.Methods: A survey of maximum responsiveness to IgE-mediated stimulation, sensitivity, and expression levels of 6 early signaling elements was performed on 36 subjects' basophils.Results: Of the 6 signaling elements, only syk and SHIP showed a correlation with maximum histamine release or cellular sensitivity. In a multiple regression, syk and SHIP together could account for 67 % of population variance, although most of the variance was explained by syk expression. The pattern of expression variance syk >> SHIP1 > SHIP2 approximate to lyn approximate to p85 approximate to cbl suggested a process that primarily modulated syk levels. IL-3 is known to modulate syk levels, but we found that a 3-day incubation with IL-3 resulted in increased expression of other signaling elements to a greater degree: cbl > SHIEP1 > SHIP2 approximate to lyn approximate to p85 >= syk, opposite the pattern in the population survey. In contrast, 18-hour stimulation with anti-IgE antibody led to marked downregulation of syk expression, modest downregulation of Fc is an element of RI expression, weak downregulation of lyn expression, and no effect on 23 other signaling elements.Conclusion: Unlike studies in mice, we conclude that expression of syk is a good preconditioning predictor of basophil function in the general population. Clinical implications: The finding that expression of syk levels may strongly influence functional responses of basophils suggests a mechanism underlying the severity of atopic diseases.