Department of Physiology, Anatomy and Genetics, Oxford University, UK.
Curr Opin Allergy Clin Immunol. 2011 Feb;11(1):33-8. doi: 10.1097/ACI.0b013e32834232b0.
This review describes recent advances in our understanding of a major Ca-entry pathway, the Ca release-activated Ca (CRAC) channel, that is central to mast cell activation.
Animals in which the genes encoding the CRAC channel have been deleted have severely compromised mast cell function and reduced allergic responses. These functional consequences reflect the ability of CRAC channels to activate a range of spatially and temporally distinct responses in mast cells, which contribute to both rapid and slow phases of an allergic response. In addition, the cells can sustain their own activation through positive feedback cycles that involve CRAC channels. Drugs that inhibit CRAC channels are proving effective in treatment of allergic responses both in vitro and in animal models of asthma.
CRAC channels comprise a new therapeutic target for combating allergies including asthma.
本篇综述描述了我们对主要钙离子内流途径——钙释放激活钙(CRAC)通道的理解的最新进展,该通道对肥大细胞的激活起核心作用。
缺失编码 CRAC 通道的基因的动物,其肥大细胞功能严重受损,过敏反应降低。这些功能后果反映了 CRAC 通道在肥大细胞中激活一系列空间和时间上不同的反应的能力,这些反应有助于过敏反应的快速和缓慢阶段。此外,细胞可以通过涉及 CRAC 通道的正反馈循环来维持自身的激活。抑制 CRAC 通道的药物在体外和哮喘动物模型中均能有效治疗过敏反应。
CRAC 通道是治疗过敏反应(包括哮喘)的新的治疗靶点。