Nitration of protein without allergenic potential triggers modulation of antioxidant response in type II pneumocytes.
Inhalation of nitrogen and reactive oxygen species (ROS) is known to induce lung inflammation, which is prevented by enzymatic and nonenzymatic antioxidant systems. These agents form nitrated allergens that were shown to enhance allergenicity. The aim of this study was to examine the influence of nitrated proteins on inflammation and antioxidant status of the lung. Ovalbumin (OVA) in nitrated form (nOVA) was intraperitoneally (ip) injected in mice for sensitization and in nitrated or unmodified form for challenge to induce allergic bronchial inflammation. To study the allergen potential of unrelated protein and verify cross-reactivity, nitrated and unmodified keyhole limpet hemocyanin (nKLH, KLH) was used for challenge. Challenge with OVA or nOVA reduced lung function and increased eosinophilia and protein content in bronchoalveolar lavage fluid (BALF). Challenge with nitrated or native OVA or KLH elevated glutathione (GSH) ratio in type II pneumocytes. Reduced mRNA expression of glutathione peroxidase (GPX) 3, glutathione reductase (GR), superoxide dismutase (SOD) 2, and catalase (CAT) was most prominent after challenge with nitrated OVA and nitrated KLH, respectively. Challenge with nOVA enhanced SOD1 mRNA reduction. Immunostaining of GPX 3 and SOD2 increased after challenge with OVA or nOVA, while reactivity of GR and reactivity of SOD2 were reduced after challenge with KLH or nKLH. SOD1 immunostaining was diminished after challenge with nonnitrated OVA or KLH. CAT immunoreaction was similar in all groups. Nitrated proteins without allergenic potential triggered mRNA reduction of antioxidants in type II cells after sensitization with a nitrated allergen but did not induce bronchial inflammation.
a Laboratory of Respiratory Cell Biology, Department of Internal Medicine, Division of Pneumology , Philipps University , Marburg.
Renate
R
Hochscheid
Nicole
N
Schreiber
Elke
E
Kotte
Petra
P
Weber
Werner
W
Cassel
Hong
H
Yang
Yingyi
Y
Zhang
Ulrich
U
Pöschl
Bernd
B
Müller
D000426:Alcohol Dehydrogenase; D000485:Allergens / Q000276:immunology*; D056809:Alveolar Epithelial Cells / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid; D002374:Catalase / Q000378:metabolism; D003429:Cross Reactions; D004802:Eosinophilia / Q000276:immunology; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006433:Hemocyanins / Q000008:administration & dosage / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D009584:Nitrogen / Q000737:chemistry; D010047:Ovalbumin / Q000008:administration & dosage / Q000737:chemistry; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000008:administration & dosage / Q000009:adverse effects; D013482:Superoxide Dismutase / Q000378:metabolism; D000099156:Superoxide Dismutase 2
D000426:Alcohol Dehydrogenase; D000485:Allergens; D000975:Antioxidants; D002374:Catalase; D005978:Glutathione; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D006433:Hemocyanins; D009584:Nitrogen; D010047:Ovalbumin; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C483598:Adh5 protein, mouse; C116888:Gpx3 protein, mouse; C032808:keyhole-limpet hemocyanin