Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
Eur J Pharmacol. 2012 Sep 5;690(1-3):1-3. doi: 10.1016/j.ejphar.2012.06.030. Epub 2012 Jul 4.
Classically, mast cells have been widely associated with allergic reactions and parasite infections, but recent studies have elucidated the important role of these cells in innate and acquired immunity, wound healing, fibrosis, and chronic inflammatory diseases. Mast cells release an impressive array of proinflammatory and immunoregulatory mediators after activation induced by either immunoglobulin-E (IgE)-dependent or IgE-independent mechanisms. Proliferation, differentiation, survival and activation of mast cells are regulated by stem cell factor (SCF), the ligand for the c-kit tyrosine kinase receptor which is expressed on the mast cell surface. Inappropriate c-kit activation causes accumulation of mast cells in tissues resulting in mastocytosis. A number of activating mutations in c-kit have recently been identified and these mutations results in aberrant mast cell growth. Thus, c-kit inhibitors may have potential application in multiple conditions associated with mast cell disorders including systemic mastocytosis, anaphylaxis, and asthma. The present perspective aims to summarize recent findings in mast cell biology and the role of c-kit tyrosine kinase inhibitors in the treatment of different mast cell associated disorders.
经典上，肥大细胞与过敏反应和寄生虫感染广泛相关，但最近的研究阐明了这些细胞在先天和获得性免疫、伤口愈合、纤维化和慢性炎症性疾病中的重要作用。肥大细胞在免疫球蛋白-E（IgE）依赖性或 IgE 非依赖性机制诱导的激活后释放大量的促炎和免疫调节介质。肥大细胞的增殖、分化、存活和激活受干细胞因子（SCF）调节，SCF 是 c-kit 酪氨酸激酶受体的配体，该受体表达在肥大细胞表面。c-kit 的不适当激活导致肥大细胞在组织中的积累，导致肥大细胞增多症。最近已经鉴定出许多 c-kit 的激活突变，这些突变导致异常的肥大细胞生长。因此，c-kit 抑制剂可能在与肥大细胞疾病相关的多种情况下具有潜在的应用，包括系统性肥大细胞增多症、过敏反应和哮喘。本综述旨在总结肥大细胞生物学的最新发现以及 c-kit 酪氨酸激酶抑制剂在治疗不同肥大细胞相关疾病中的作用。
