Signature current of SO2-induced bronchitis in rabbit.
To investigate abnormalities of airway epithelial ion transport underlying chronic inflammatory airway diseases, we performed electrophysiological, histological, and molecular biological experiments using rabbits exposed to SO2 as a model of bronchitis. By comparison with control, the SO2-exposed trachea exhibited decreased short circuit current (Isc) and conductance associated with increased potential difference. In normal trachea, apical ATP induced a transient Isc activation followed by a suppression, whereas the bronchitis model exhibited a prolonged activation without suppression. This pathological ATP response was abolished by diphenylamine 2-carboxylate or Cl--free bath solution. A significant increase in net Cl- flux toward the lumen was observed after ATP in our bronchitis model. Isoproterenol or adenosine evoked a sustained Isc increase in SO2-exposed, but not in normal, tracheas. The Northern blot analysis showed a strong expression of cystic fibrosis transmembrane conductance regulator (CFTR) mRNA in SO2-exposed epithelium. The immunohistochemical study revealed a positive label of CFTR on cells located luminally only in SO2-exposed rabbits. We concluded that the prolonged ATP response in our bronchitis model was of a superimposed normal and adenosine-activated current. The latter current was also activated by isoproterenol and appeared as a signature current for the bronchitis model airway. This was likely mediated by CFTR expressed in the course of chronic inflammation.
Iwase
N
N
First Department of Internal Medicine, Tohoku University School of Medicine, Aoba-ku, Sendai, Japan.
Sasaki
T
T
Shimura
S
S
Fushimi
T
T
Okayama
H
H
Hoshi
H
H
Irokawa
T
T
Sasamori
K
K
Takahashi
K
K
Shirato
K
K
D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001991:Bronchitis / Q000139:chemically induced / Q000378:metabolism*; D018118:Chloride Channels / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000032:analysis / Q000235:genetics; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011817:Rabbits; D013458:Sulfur Dioxide / Q000633:toxicity*
D018118:Chloride Channels; D013458:Sulfur Dioxide; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D000241:Adenosine; D007545:Isoproterenol