Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine, Boston, MA 02111, USA.
Curr Pharm Des. 2012;18(16):2261-77. doi: 10.2174/138161212800165997.
Mast cells are important in the development of allergic and anaphylactic reactions, but also in acquired and innate immunity. There is also increasing evidence that mast cells participate in inflammatory diseases, where they can be activated by non-allergic triggers, such as neuropeptides and cytokines, often having synergistic effects as in the case of substance P (SP) and IL-33. Secretion of vasoactive mediators, cytokines and proteinases contribute to the development of coronary artery disease (CAD), as well as to diet-induced obesity and the metabolic syndrome. Mast cells may be able to orchestrate such different biological processes through their ability to release pro-inflammatory mediators selectively without the degranulation typical of allergic reactions. Recent evidence suggests that mitochondrial uncoupling protein 2 (UCP2) and mitochondrial translocation regulate mast cell degranulation, but not selective mediator release. Better understanding of these two processes and how mast cells exert both immunostimulatory and immunosuppressive actions could lead to the development of inhibitors of release of specific mediators with novel therapeutic applications.
肥大细胞在过敏和过敏反应的发展中很重要,但也在获得性和先天性免疫中发挥作用。越来越多的证据表明,肥大细胞参与炎症性疾病,在这些疾病中,它们可以被非过敏触发物激活,如神经肽和细胞因子,通常具有协同作用,如 P 物质 (SP) 和 IL-33。血管活性介质、细胞因子和蛋白酶的分泌导致冠状动脉疾病 (CAD) 的发展,以及饮食诱导的肥胖和代谢综合征。肥大细胞可能能够通过其选择性释放促炎介质而不发生典型过敏反应的脱颗粒来协调如此不同的生物学过程。最近的证据表明,线粒体解偶联蛋白 2 (UCP2) 和线粒体易位调节肥大细胞脱颗粒,但不调节选择性介质释放。更好地理解这两个过程以及肥大细胞如何发挥免疫刺激和免疫抑制作用,可能会导致开发具有新治疗应用的特定介质释放抑制剂。