INDUCIBLE NITRIC-OXIDE SYNTHASE EXPRESSION IS REDUCED IN CYSTIC-FIBROSIS MURINE AND HUMAN AIRWAY EPITHELIAL-CELLS

It has been reported that exhaled nitric oxide levels are reduced in c ystic fibrosis (CF) patients. We have examined the inducible isoform o f nitric oxide synthase (iNOS) in the airways by immunostaining and fo und that iNOS is constitutively expressed in the airway epithelia of n on-CF mouse and human tissues but essentially absent in the epithelium of CF airways. We explored potential consequences of lost iNOS expres sion and found that iNOS inhibition significantly increases mouse nasa l trans-epithelial potential difference, and hindered the ability of e xcised mouse lungs to prevent growth of Pseudomonas aeruginosa. The ab sence of continuous nitric oxide production in epithelial cells of CF airways may play a role in two CF-associated characteristics: hyperabs orption of sodium and susceptibility to bacterial infections.