SIGNATURE CURRENT OF SO2-INDUCED BRONCHITIS IN RABBIT

To investigate abnormalities of airway epithelial ion transport underl ying chronic inflammatory airway diseases, we performed electrophysiol ogical, histological, and molecular biological experiments using rabbi ts exposed to SO2 as a model of bronchitis. By comparison with control , the SO2-exposed trachea exhibited decreased short circuit current (I sc) and conductance associated with increased potential difference. In normal trachea, apical ATP induced a transient Isc activation followe d by a suppression, whereas the bronchitis model exhibited a prolonged activation without suppression. This pathological ATP response was ab olished by diphenylamine 2-carboxylate or Cl--free bath solution. A si gnificant increase in net Cl- flux toward the lumen was observed after ATP in our bronchitis model. Isoproterenol or adenosine evoked a sust ained Isc increase in SO2-exposed, but not in normal, tracheas. The No rthern blot analysis showed a strong expression of cystic fibrosis tra nsmembrane conductance regulator (CFTR) mRNA in SO2-exposed epithelium . The immunohistochemical study revealed a positive label of CFTR on c ells located luminally only in SO2-exposed rabbits. We concluded that the prolonged ATP response in our bronchitis model was of a superimpos ed normal and adenosine-activated current. The latter current was also activated by isoproterenol and appeared as a signature current for th e bronchitis model airway. This was likely mediated by CFTR expressed in the course of chronic inflammation.