Rethinking the central role of mast cells in virally mediated asthma exacerbations.
Rethinking the central role of mast cells in virally mediated asthma exacerbations.
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重新考虑肥大细胞在病毒介导的哮喘恶化中的核心作用。
DOI：
10.1016/j.anai.2022.03.029
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发表时间：
2022-12
影响因子：
5.9
通讯作者：
Borish, Larry
中科院分区：
文献类型：
--
作者：
Borish, Larry
一代人以前，过敏性疾病被认为是“I型”超敏性疾病，其特征在于过敏/IgE致敏，其中过敏原结合IgE包被的肥大细胞（和嗜碱性粒细胞），产生即时和晚期反应。事实上，嗜酸性粒细胞被认为除了通过酶促降解组胺和半胱氨酰白三烯来“清理”肥大细胞之外没有什么作用。随后的研究恰当地确立了嗜酸性粒细胞在产生哮喘的许多炎症和生理特征中的重要作用。这种以嗜酸性粒细胞为中心的模型导致了基于指南的治疗方法的转变，皮质类固醇（CCS）占据主导地位，最近，白细胞介素（IL）-5和IL-5受体靶向生物制剂的出现。目前的模式已经达到了肥大细胞经常赚取的地步，最好的，在我们思考哮喘发病机制通过参考。然而，值得注意的是，CCS虽然不能阻断肥大细胞脱颗粒，但确实可以减轻过敏季节发生的气道肥大细胞激增，并且肥大细胞上IL-5受体的表达作为IL-5靶向生物制剂有效性的合理机制的作用尚未得到充分探讨。这包括观察到，虽然嗜酸性粒细胞靶向治疗可能非常有效，但大量患者对这些方法没有反应。对这些失败的基础的充分讨论超出了本论文的范围，但这种失败确实包括重新考虑“低级”肥大细胞的作用的必要性。最早让我们重新思考肥大细胞的研究之一是伊马替尼（一种肥大细胞相关酪氨酸激酶ckit的抑制剂）治疗严重哮喘的随机试验。该代理商生产
A generation ago allergic diseases were viewed as “Type I” hypersensitivity disorders characterized by allergic/IgE sensitization with allergen binding to IgE-coated mast cells (and basophils) producing an immediate and late phase response. Indeed, eosinophils were envisioned as having little more of a role than to “clean up” after the mast cell by enzymatically degrading histamine and cysteinyl leukotrienes. Subsequent investigations appropriately established an essential role for the eosinophil in producing many of the inflammatory and physiological features of asthma. This eosinophil-centric model led to a shift in guidelines-based therapies with a dominant role for corticosteroids (CCS) and, more recently, the emergence of interleukin (IL)-5-and IL-5 receptor-targeting biologics. This current paradigm has reached the point where mast cells often earn, at best, passing reference in our thinking regarding asthma pathogenesis. It should be noted, however, that that while not blocking mast cell degranulation, CCS do mitigate the surge in airway mast cells that occurs with allergy seasons and that a role for the expression of IL-5 receptors on mast cells as a plausible mechanism for efficacy of IL-5-targeting biologics has not been adequately explored.Recent studies, however, argue for mast cells having a more central role in asthma. This includes observations that although eosinophil-targeting therapies can be quite effective, a remarkable number of patients fail to respond to these approaches. A full discussion of the basis for these failures is beyond the scope of this treatise but this failure does include the need for reconsideration of the role of the “lowly” mast cell. One of the first studies to reengage our thinking about mast cells was a randomized trial of imatinib–an inhibitor of the mast cell-associated tyrosine kinase ckit–in severe asthma. This agent produced
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伊马替尼在严重难治性哮喘患者中抑制试剂盒。
DOI：
10.1056/nejmoa1613125
发表时间：
2017-05-18
期刊：
The New England journal of medicine
影响因子：
--
作者：
Cahill KN;Katz HR;Cui J;Lai J;Kazani S;Crosby-Thompson A;Garofalo D;Castro M;Jarjour N;DiMango E;Erzurum S;Trevor JL;Shenoy K;Chinchilli VM;Wechsler ME;Laidlaw TM;Boyce JA;Israel E
通讯作者：
Israel E
DOI：
10.1016/j.jaci.2020.01.035
发表时间：
2020-09
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Heymann PW;Platts-Mills TAE;Woodfolk JA;Borish L;Murphy DD;Carper HT;Conaway MR;Steinke JW;Muehling L;Gerald Teague W;Kennedy JL;Irani AM;McGraw MD;Early SV;Wheatley LM;Adams AP;Turner RB
通讯作者：
Turner RB
DOI：
10.1164/ajrccm.159.3.9801052
发表时间：
1999-03-01
影响因子：
24.7
作者：
Rakes, CP;Arruda, E;Heymann, PW
通讯作者：
Heymann, PW
影响因子：
14.2
作者：
Zambrano, JC;Carper, HT;Heymann, PW
通讯作者：
Heymann, PW
DOI：
10.1165/rcmb.2009-0244oc
发表时间：
2010-12-01
影响因子：
6.4
作者：
Lachowicz-Scroggins, Marrah E.;Boushey, Homer A.;Widdicombe, Jonathan H.
通讯作者：
Widdicombe, Jonathan H.