Leukocyte nicotinamide adenine dinucleotide phosphate-reduced oxidase is required for isocyanate-induced lung inflammation

作者：Liu Si Yen; Wang Wei Zhi; Yen Chia Liang; Tsai Ming Yi; Yang Pei Wen; Wang Jiu Yao; Ho Chun Yi; Shieh Chi Chang^*

来源：Journal of Allergy and Clinical Immunology, 2011, 127(4): 1014-1023.

DOI：10.1016/j.jaci.2010.12.008

• NADPH oxidase
• redox regulation
• toluene diisocyanate
• leukocyte
• lung inflammation

Background: 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.
Objectives: 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.
Methods: 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.
Results: 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.
Conclusion: Leukocyte NADPH oxidase is an essential regulator in TDI-induced airway inflammation through redox modification of immune responses. (J Allergy Clin Immunol 2011;127:1014-23.)

• 出版日期2011-4