Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Allergol Int. 2011 Sep;60(3):259-66. doi: 10.2332/allergolint.09-OA-0167. Epub 2011 Feb 25.
Zinc is an essential element required for the cell metabolism, including gene transcription, signal transduction, immunity, and apoptosis. The pathophysiological role of zinc in asthma, however, is not entirely clear. Mast cells have been implicated in atopic asthma, and zinc deprivation has been reported to reduce mast cell activation. Here, we investigate the effects of a zinc chelator, N,N,N',N'-tetrakis (2-pyridyl-methyl) ethylenediamine (TPEN), on asthmatic responses in mouse models of ovalbumin (OVA)-induced airway hyperresponsiveness and allergic airway inflammation.
Mice were sensitized with OVA with or without the adjuvant aluminum hydroxide (alum) and subjected to OVA exposure with or without treatment of TPEN. Cell profiles and cytokine levels in bronchoalveolar lavage (BAL) fluids, airway responsiveness to inhaled acetylcholine, and goblet cell hyperplasia after allergen exposure were assessed.
In mice sensitized to OVA without alum, TPEN significantly suppressed airway hyperresponsiveness and eosinophilia in BAL fluids. TPEN also attenuated the upregulation of TNFα, IL-13 and IL-4 in BAL fluids and goblet cell hyperplasia after OVA exposure. By contrast, in mice sensitized to OVA with alum, TPEN suppressed eosinophilia in BAL fluids but not airway hyperresponsiveness and goblet cell hyperplasia.
In pulmonary allergic inflammation induced in mice immunized with antigen without alum, zinc chelator inhibits airway inflammation and hyperresponsiveness. These findings suggest that zinc may be a therapeutic target of allergic asthma.
锌是细胞代谢所必需的元素，包括基因转录、信号转导、免疫和细胞凋亡。然而，锌在哮喘中的病理生理作用尚不完全清楚。肥大细胞被认为与特应性哮喘有关，并且据报道锌剥夺会减少肥大细胞的激活。在这里，我们研究了锌螯合剂 N,N,N',N'-四（2-吡啶基甲基）乙二胺（TPEN）对卵清蛋白（OVA）诱导的气道高反应性和变应性气道炎症的小鼠模型中哮喘反应的影响。
用 OVA 联合或不联合佐剂氢氧化铝（alum）对小鼠进行致敏，并在给予或不给予 TPEN 处理的情况下进行 OVA 暴露。评估支气管肺泡灌洗液（BAL）中的细胞谱和细胞因子水平、气道对吸入乙酰胆碱的反应性以及过敏原暴露后的杯状细胞增生。
在未用 alum 致敏的 OVA 小鼠中，TPEN 显著抑制气道高反应性和 BAL 液中的嗜酸性粒细胞增多。TPEN 还可减弱 BAL 液中 TNFα、IL-13 和 IL-4 的上调以及 OVA 暴露后的杯状细胞增生。相比之下，在用 alum 致敏的 OVA 小鼠中，TPEN 抑制 BAL 液中的嗜酸性粒细胞增多，但不抑制气道高反应性和杯状细胞增生。
在无 alum 免疫的小鼠中，抗原诱导的肺变应性炎症中，锌螯合剂抑制气道炎症和高反应性。这些发现表明锌可能是变应性哮喘的治疗靶点。
