Mast cells (MCs) are granular cells of the innate immune system which develop from CD34+/CD117+ progenitors and play a role in orchestrating adaptive immune responses. They have a well-known role in allergic reactions following immunoglobulin (Ig)E-mediated activation of the cell-surface expressed IgE high-affinity receptor (FcεRI). MCs can also respond to various other stimuli due to the expression of a variety of receptors including toll-like receptors (TLRs), immunoglobulin (IgG) receptors (FcγR), complement receptors such as C5a (CD88) expressed by skin MCs, neuropeptides receptors including nerve growth factor receptor, (NGFR), cytokines receptors such as (IL)-1R and IL-3R, and chemokines receptors including CCR-1 and CCR-3. MCs release three groups of mediators upon degranulation differentiated according to their chemical composition, storage, and time to release. These include preformed mediators (mainly histamine, tryptase, and chymase), de novo synthesized mediators such as prostaglandin (PG)D2, leukotriene (LT)B4 and LTD4, and cytokines including IL-1β, IL-3, tumor necrosis factor (TNF)α, and transforming growth factor(TGF)-β. Emerging evidence indicates a role for IgE-independent MC activation in the late-stage asthmatic response as well as in non-allergic airway diseases including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and lung cancer. MC infiltration/activation has been reported in some, but not all, studies of lung cancer. MC-derived TNF-α possesses tumor-suppressive activity while IL-1β supports tumor progression and metastasis. In IPF lungs, an increase in density of tryptase- and chymase-positive MCs (MCTC) and overexpression of TGF-β support the fibrosis progression. MC-derived chymase activates latent TGF-β that induces the differentiation of fibroblasts to matrix-producing myofibroblasts. In summary, increasing evidence highlights a critical role of MCs in non-allergic diseases that may indicate new approaches for therapy.

中文翻译：

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肥大细胞在 IgE 依赖性肺部疾病中的作用。


肥大细胞 (MC) 是先天免疫系统的颗粒细胞，由 CD34+/CD117+ 祖细胞发育而来，在协调适应性免疫反应中发挥作用。它们在免疫球蛋白 (Ig)E 介导的细胞表面表达的 IgE 高亲和力受体 (FcεRI) 激活后的过敏反应中发挥着众所周知的作用。由于多种受体的表达，MC​​还可以对各种其他刺激做出反应，包括Toll样受体（TLR）、免疫球蛋白（IgG）受体（FcγR）、皮肤MC表达的补体受体（例如C5a（CD88））、神经肽受体包括神经生长因子受体（NGFR）、细胞因子受体（例如（IL）-1R和IL-3R）以及趋化因子受体（包括CCR-1和CCR-3）。 MC 在脱颗粒时释放三组介质，根据其化学成分、储存和释放时间进行区分。这些包括预先形成的介质（主要是组胺、类胰蛋白酶和糜酶）、从头合成的介质，例如前列腺素 (PG)D2、白三烯 (LT)B4 和 LTD4，以及细胞因子，包括 IL-1β、IL-3、肿瘤坏死因子 (TNF) )α、转化生长因子(TGF)-β。新的证据表明，独立于 IgE 的 MC 激活在晚期哮喘反应以及非过敏性气道疾病（包括慢性阻塞性肺病 (COPD)、特发性肺纤维化 (IPF) 和肺癌）中发挥作用。一些（但不是全部）肺癌研究报告了 MC 浸润/激活。 MC 衍生的 TNF-α 具有肿瘤抑制活性，而 IL-1β 支持肿瘤进展和转移。在 IPF 肺部，类胰蛋白酶和糜酶阳性 MC (MCTC) 密度的增加以及 TGF-β 的过度表达支持纤维化进展。 MC 衍生的食糜酶激活潜在的 TGF-β，诱导成纤维细胞分化为产生基质的肌成纤维细胞。总之，越来越多的证据强调了 MC 在非过敏性疾病中的关键作用，这可能预示着新的治疗方法。