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Mast cells as a unique hematopoietic lineage and cell system: From Paul Ehrlich's visions to precision medicine concepts.
Theranostics ( IF 12.4 ) Pub Date : 2020-8-29 , DOI: 10.7150/thno.46719
Peter Valent 1 , Cem Akin 2 , Karin Hartmann 3 , Gunnar Nilsson 4 , Andreas Reiter 5 , Olivier Hermine 6 , Karl Sotlar 7 , Wolfgang R Sperr 1 , Luis Escribano 8 , Tracy I George 9 , Hanneke C Kluin-Nelemans 10 , Celalettin Ustun 11 , Massimo Triggiani 12 , Knut Brockow 13 , Jason Gotlib 14 , Alberto Orfao 8 , Petri T Kovanen 15 , Emir Hadzijusufovic 1, 16 , Irina Sadovnik 1 , Hans-Peter Horny 17 , Michel Arock 18 , Lawrence B Schwartz 19 , K Frank Austen 20 , Dean D Metcalfe 21 , Stephen J Galli 22
Affiliation  

The origin and functions of mast cells (MCs) have been debated since their description by Paul Ehrlich in 1879. MCs have long been considered 'reactive bystanders' and 'amplifiers' in inflammatory processes, allergic reactions, and host responses to infectious diseases. However, knowledge about the origin, phenotypes and functions of MCs has increased substantially over the past 50 years. MCs are now known to be derived from multipotent hematopoietic progenitors, which, through a process of differentiation and maturation, form a unique hematopoietic lineage residing in multiple organs. In particular, MCs are distinguishable from basophils and other hematopoietic cells by their unique phenotype, origin(s), and spectrum of functions, both in innate and adaptive immune responses and in other settings. The concept of a unique MC lineage is further supported by the development of a distinct group of neoplasms, collectively referred to as mastocytosis, in which MC precursors expand as clonal cells. The clinical consequences of the expansion and/or activation of MCs are best established in mastocytosis and in allergic inflammation. However, MCs have also been implicated as important participants in a number of additional pathologic conditions and physiological processes. In this article, we review concepts regarding MC development, factors controlling MC expansion and activation, and some of the fundamental roles MCs may play in both health and disease. We also discuss new concepts for suppressing MC expansion and/or activation using molecularly-targeted drugs.

中文翻译:


肥大细胞作为独特的造血谱系和细胞系统:从保罗·埃利希的愿景到精准医学概念。



自从 Paul Ehrlich 于 1879 年描述肥大细胞 (MC) 以来,其起源和功能一直存在争议。长期以来,肥大细胞一直被认为是炎症过程、过敏反应和宿主对传染病的反应中的“反应性旁观者”和“放大器”。然而,在过去的 50 年里,人们对 MC 的起源、表型和功能的了解有了显着的增长。现在已知MCs源自多能造血祖细胞,它们通过分化和成熟的过程,形成存在于多个器官中的独特的造血谱系。特别是,MC 因其独特的表型、起源和功能谱而与嗜碱性粒细胞和其他造血细胞区分开来,无论是在先天性免疫反应还是适应性免疫反应以及其他环境中。独特的 MC 谱系的概念得到了一组独特肿瘤的发展的进一步支持,这些肿瘤统称为肥大细胞增多症,其中 MC 前体扩展为克隆细胞。 MC 扩张和/或激活的临床后果在肥大细胞增多症和过敏性炎症中得到了最好的证实。然而,MC 也被认为是许多其他病理状况和生理过程的重要参与者。在本文中,我们回顾了有关 MC 发育、控制 MC 扩张和激活的因素以及 MC 在健康和疾病中可能发挥的一些基本作用的概念。我们还讨论了使用分子靶向药物抑制 MC 扩张和/或激活的新概念。
更新日期:2020-08-30
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