Modena Brian D, Dazy Kristen, White Andrew A
Division of Allergy, Asthma and Immunology, Scripps Clinic, San Diego, Calif; Scripps Translational Science Institute, The Scripps Research Institute, La Jolla, Calif.
Division of Allergy, Asthma and Immunology, Scripps Clinic, San Diego, Calif.
Transl Res. 2016 Aug;174:98-121. doi: 10.1016/j.trsl.2016.02.011. Epub 2016 Feb 24.
In a process known as overt degranulation, mast cells can release all at once a diverse array of products that are preformed and present within cytoplasmic granules. This occurs typically within seconds of stimulation by environmental factors and allergens. These potent, preformed mediators (ie, histamine, heparin, serotonin, and serine proteases) are responsible for the acute symptoms experienced in allergic conditions such as allergic conjunctivitis, allergic rhinitis, allergy-induced asthma, urticaria, and anaphylaxis. Yet, there is reason to believe that the actions of mast cells are important when they are not degranulating. Mast cells release preformed mediators and inflammatory cytokines for periods after degranulation and even without degranulating at all. Mast cells are consistently seen at sites of chronic inflammation, including nonallergic inflammation, where they have the ability to temper inflammatory processes and shape tissue morphology. Mast cells can trigger actions and chemotaxis in other important immune cells (eg, eosinophils and the newly discovered type 2 innate lymphocytes) that then make their own contributions to inflammation and disease. In this review, we will discuss the many known and theorized contributions of mast cells to allergic diseases, focusing on several prototypical allergic respiratory and skin conditions: asthma, chronic rhinosinusitis, aspirin-exacerbated respiratory disease, allergic conjunctivitis, atopic dermatitis, and some of the more common medication hypersensitivity reactions. We discuss traditionally accepted roles that mast cells play in the pathogenesis of each of these conditions, but we also delve into new areas of discovery and research that challenge traditionally accepted paradigms.
在一个被称为明显脱颗粒的过程中，肥大细胞可以一次性释放一系列预先形成并存在于细胞质颗粒中的产物。这通常在环境因素和过敏原刺激后的几秒钟内发生。这些强大的、预先形成的介质（即组胺、肝素、5-羟色胺和丝氨酸蛋白酶）是导致过敏性疾病（如过敏性结膜炎、过敏性鼻炎、过敏性哮喘、荨麻疹和过敏反应）中出现急性症状的原因。然而，有理由相信，肥大细胞在不发生脱颗粒时的作用也很重要。肥大细胞在脱颗粒后甚至在根本不发生脱颗粒的情况下，会在一段时间内释放预先形成的介质和炎性细胞因子。在包括非过敏性炎症在内的慢性炎症部位，经常可以看到肥大细胞，它们有能力调节炎症过程并塑造组织形态。肥大细胞可以触发其他重要免疫细胞（如嗜酸性粒细胞和新发现的2型固有淋巴细胞）的行动和趋化性，这些细胞随后会对炎症和疾病做出自己的贡献。在这篇综述中，我们将讨论肥大细胞对过敏性疾病的许多已知和理论上的贡献，重点关注几种典型的过敏性呼吸道和皮肤疾病：哮喘、慢性鼻窦炎、阿司匹林诱发的呼吸道疾病、过敏性结膜炎、特应性皮炎以及一些更常见的药物过敏反应。我们将讨论肥大细胞在这些疾病的发病机制中传统上被认可的作用，但我们也会深入探讨挑战传统公认范式的新发现和研究领域。
