Institute of Basic Medicine, National Cheng Kung University Medical College, Tainan, Taiwan.
J Allergy Clin Immunol. 2011 Apr;127(4):1014-23. doi: 10.1016/j.jaci.2010.12.008. Epub 2011 Jan 26.
Isocyanates are low-molecular-weight compounds noted for inducing occupational and environmental asthma. Isocyanate-induced lung disease, an oxidant stress-dependent pulmonary inflammation, is the leading cause of occupational asthma.
To address the role of leukocyte-produced oxidants in airway inflammation induced by toluene diisocyanate (TDI), and to elucidate the role of leukocyte nicotinamide adenine dinucleotide phosphate-reduced (NADPH) oxidase in pathogenesis by TDI.
Wild-type mice and NADPH oxidase-deficient mice (neutrophil cytosolic factor 1 mutant, Ncf1(-/-)) were intranasally injected, challenged with inhalatory TDI, and then investigated for lung inflammation.
Cell infiltration in lung tissue and leukocytes in bronchoalveolar lavage, airway reactivity to a methacholine challenge, and TDI-induced inflammatory cytokine expression and nuclear factor activation in the lung tissue were all markedly lower in Ncf1(-/-) mice. Wild-type mice treated with blocking antibodies against CD4 and IL-17 showed markedly lower TDI-induced airway hyperresponsiveness.
Leukocyte NADPH oxidase is an essential regulator in TDI-induced airway inflammation through redox modification of immune responses.
异氰酸酯是一种低分子量化合物，其特点是能引起职业性和环境性哮喘。异氰酸酯引起的肺部疾病，一种依赖于氧化应激的肺部炎症，是职业性哮喘的主要原因。
探讨白细胞产生的氧化剂在甲苯二异氰酸酯（TDI）诱导的气道炎症中的作用，并阐明白细胞烟酰胺腺嘌呤二核苷酸磷酸还原酶（NADPH）氧化酶在 TDI 发病机制中的作用。
采用野生型小鼠和 NADPH 氧化酶缺陷型小鼠（中性粒细胞胞质因子 1 突变型，Ncf1(-/-)），经鼻腔内注射，吸入 TDI 进行挑战，然后对肺炎症进行研究。
Ncf1(-/-)小鼠肺组织细胞浸润和支气管肺泡灌洗液中的白细胞、气道对乙酰甲胆碱激发的反应性以及 TDI 诱导的肺组织中炎症细胞因子表达和核因子激活均明显降低。用针对 CD4 和 IL-17 的阻断抗体处理的野生型小鼠，TDI 诱导的气道高反应性明显降低。
白细胞 NADPH 氧化酶通过对免疫反应的氧化还原修饰，是 TDI 诱导的气道炎症的一个重要调节因子。
