Huber Michael, Gibbs Bernhard F
Institute of Biochemistry and Molecular Immunology, RWTH Aachen University, University Clinic, Aachen, Germany.
Medway School of Pharmacy, University of Kent, Central Avenue, Chatham Maritime, Kent, United Kingdom.
Mol Immunol. 2015 Jan;63(1):32-7. doi: 10.1016/j.molimm.2014.02.017. Epub 2014 Mar 25.
IgE-mediated, antigen-triggered activation of mast cells and basophils often results in bell-shaped dose-response curves for the release of various pro-inflammatory mediators. The degree of suppression of mediator release observed following supra-optimal stimulation varies widely for different allergens as well as for different experimental agents that cause crosslinking of high-affinity IgE receptors (FcɛRI) on these cells. While the reasons for these differences have not yet been resolved it has become increasingly apparent that supra-optimal stimulation in many cases causes a shift in the balance of stimulatory and inhibitory signal transduction mechanisms arising from FcɛRI triggering. In particular, the lipid phosphatase SHIP1 has been shown to be centrally involved in explaining the bell-shaped phenomena in both mast cells and basophils in different species and appears to play a fundamental role in limiting the IgE responsiveness of these allergic effector cells. Elucidating the nature of this inhibitory signaling pathway may provide crucial knowledge in order to optimize desensitization strategies in the treatment of allergic diseases.
IgE介导的、抗原触发的肥大细胞和嗜碱性粒细胞活化通常会导致各种促炎介质释放呈现钟形剂量反应曲线。超最佳刺激后观察到的介质释放抑制程度，对于不同过敏原以及导致这些细胞上高亲和力IgE受体（FcɛRI）交联的不同实验试剂而言，差异很大。虽然这些差异的原因尚未得到解决，但越来越明显的是，在许多情况下，超最佳刺激会导致FcɛRI触发产生的刺激和抑制信号转导机制的平衡发生转变。特别是，脂质磷酸酶SHIP1已被证明在解释不同物种肥大细胞和嗜碱性粒细胞中的钟形现象方面起着核心作用，并且似乎在限制这些过敏效应细胞的IgE反应性方面发挥着基本作用。阐明这种抑制性信号通路的性质可能为优化过敏性疾病治疗中的脱敏策略提供关键知识。
