Targeting c-kit in the therapy of mast cell disorders: Current update
Targeting c-kit in the therapy of mast cell disorders: Current update
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DOI：
10.1016/j.ejphar.2012.06.030
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发表时间：
2012-09-05
影响因子：
5
通讯作者：
El-Agamy, Dina S.
中科院分区：
文献类型：
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作者：
El-Agamy, Dina S.
肥大细胞通常与过敏反应和寄生虫感染有关，但最近的研究已经阐明了这些细胞在先天性和获得性免疫、伤口愈合、纤维化和慢性炎症性疾病中的重要作用。肥大细胞释放一系列令人印象深刻的促炎和免疫调节介质激活后诱导免疫球蛋白E（IgE）依赖性或IgE非依赖性机制。肥大细胞的增殖、分化、存活和活化受干细胞因子（SCF）调节，干细胞因子是表达于肥大细胞表面的c-kit酪氨酸激酶受体的配体。不适当的c-kit激活导致肥大细胞在组织中积聚，从而导致肥大细胞增多症。最近已经鉴定了c-kit中的许多激活突变，并且这些突变导致异常肥大细胞生长。因此，c-kit抑制剂可能在与肥大细胞疾病相关的多种疾病中具有潜在的应用，包括系统性肥大细胞增多症、过敏反应和哮喘。目前的观点旨在总结肥大细胞生物学的最新发现和c-kit酪氨酸激酶抑制剂在不同的肥大细胞相关疾病的治疗中的作用。(C)2012 Elsevier B. V.保留所有权利。
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. (C) 2012 Elsevier B.V. All rights reserved.