CCSP modulates airway dysfunction and host responses in an Ova-challenged mouse model.
Clara cell secretory protein (CCSP) is synthesized by nonciliated bronchiolar cells in the lung and modulates lung inflammation to infection. To determine the role of CCSP in the host response to allergic airway disease, CCSP-deficient [(-/-)] mice were immunized twice with ovalbumin (Ova) and challenged by Ova (2 or 5 mg/m(3)) aerosol. After 2, 3, and 5 days of Ova aerosol challenge (6 h/day), airway reactivity was increased in CCSP(-/-) mice compared with wild-type [CCSP(+/+)] mice. Neutrophils were markedly increased in the bronchoalveolar lavage fluid of CCSP(-/-) Ova mice, coinciding with increased myeloperoxidase activity and macrophage inflammatory protein-2 levels. Lung histopathology and inflammation were increased in CCSP(-/-) compared with wild-type mice after Ova challenge. Mucus production, as assessed by histological staining, was increased in the airway epithelium of CCSP(-/-) Ova mice compared with that in CCSP(+/+) Ova mice. These data suggest a role for CCSP in airway reactivity and the host response to allergic airway inflammation and provide further evidence for the role of the airway epithelium in regulating airway responses in allergic disease.
Wang
S Z
SZ
Asthma and Pulmonary Immunology Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87185, USA.
Rosenberger
C L
CL
Espindola
T M
TM
Barrett
E G
EG
Tesfaigzi
Y
Y
Bice
D E
DE
Harrod
K S
KS
D000818:Animals; D001249:Asthma / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology; D008168:Lung / Q000473:pathology / Q000503:physiopathology*; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology*; D009195:Peroxidase / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D014598:Uteroglobin
D016085:Bronchoconstrictor Agents; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D004791:Enzyme Inhibitors; D011506:Proteins; C556389:SCGB1A1 protein, human; C556390:Scgb1a1 protein, mouse; D016210:Methacholine Chloride; D010047:Ovalbumin; D014598:Uteroglobin; D009195:Peroxidase