title: Leukocyte nicotinamide adenine dinucleotide phosphate-reduced oxidase is required for isocyanate-induced lung inflammation.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Leukocyte NADPH oxidase is an essential regulator in TDI-induced airway inflammation through redox modification of immune responses.
authors.affiliation: Institute of Basic Medicine, National Cheng Kung University Medical College, Tainan, Taiwan.
authors.forename: Si-Yen
authors.initials: SY
authors.lastname: Liu
authors.forename: Wei-Zhi
authors.initials: WZ
authors.lastname: Wang
authors.forename: Chia-Liang
authors.initials: CL
authors.lastname: Yen
authors.forename: Ming-Yi
authors.initials: MY
authors.lastname: Tsai
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Yang
authors.forename: Jiu-Yao
authors.initials: JY
authors.lastname: Wang
authors.forename: Chun-Yi
authors.initials: CY
authors.lastname: Ho
authors.forename: Chi-Chang
authors.initials: CC
authors.lastname: Shieh
mesh_terms: D000818:Animals; D005260:Female; D007962:Leukocytes / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000276:immunology / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000276:immunology*; D011014:Pneumonia / Q000139:chemically induced / Q000201:enzymology* / Q000276:immunology; D021381:Protein Transport / Q000276:immunology; D014051:Toluene 2,4-Diisocyanate / Q000276:immunology / Q000378:metabolism / Q000633:toxicity*
chemical_list: D051267:NF-E2-Related Factor 2; D014051:Toluene 2,4-Diisocyanate; D019255:NADPH Oxidases