Increased oxidative stress in the airway and development of allergic inflammation in a mouse model of asthma.
BACKGROUND
The exact pathogenic role of oxidative stress in the development of allergic airway inflammation is still largely unknown.


OBJECTIVE
To investigate a possible link between increased pulmonary oxidative stress and the pivotal features of asthma during the mounting of an allergic inflammatory response.


METHODS
To determine the relationship between oxidative stress and allergic inflammatory responses, we evaluated the sequential kinetics of oxidative stress in the lung, the development of airway inflammation, mucin hypersecretion, and airway hyperresponsiveness (AHR) in an ovalbumin (OVA)-sensitized and challenged mouse with and without antioxidant. Parameters were measured at 9 points for more than 28 days, starting from the first day of OVA challenge with or without antioxidant treatment. The ratio of reduced to oxidized glutathione in the lungs and levels of intracellular reactive oxygen species (ROS) in the bronchial epithelium were serially measured. Bronchoalveolar lavage fluid cells, histopathologic features, and AHR were analyzed at the same time points.


RESULTS
The reduced to oxidized glutathione ratio was reduced from immediately after OVA challenge to day 1, remained at this level until day 1, and rapidly recovered to the normal level after more than 2 days. Intracellular ROS levels in the bronchial epithelium followed similar kinetics. The inflammatory cells in bronchoalveolar lavage fluid reached a maximum of 3 days and decreased progressively thereafter. Histopathologic examination revealed that substantial airway inflammation persisted through day 28. The proportion of mucin-producing epithelial cells significantly increased after day 1, reached a maximum at day 3, and remained at this level until day 5. The AHR peaked on day 1 and normalized within 5 days. The pretreatment of antioxidant significantly reduced not only the increased ROS levels but also development of other phenotypes of asthma.


CONCLUSIONS
These results indicate that increased oxidative stress in the lung precedes other pivotal phenotypes of allergic airway disease, suggesting a critical role for increased oxidative stress in the induction of allergic airway inflammation.
Park
Chan-Sun
CS
Division of Allergy and Clinical Immunology, Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Kim
Tae-Bum
TB
Lee
Ki-Young
KY
Moon
Keun-Ai
KA
Bae
Yun-Jeong
YJ
Jang
Min Kyoung
MK
Cho
You Sook
YS
Moon
Hee-Bom
HB
D000111:Acetylcysteine / Q000008:administration & dosage; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage; D005978:Glutathione / Q000031:analogs & derivatives / Q000032:analysis; D007114:Immunization; D007249:Inflammation; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009077:Mucins / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000473:pathology / Q000502:physiology*
D016166:Free Radical Scavengers; D009077:Mucins; D010047:Ovalbumin; D005978:Glutathione; D000111:Acetylcysteine