iNOS expression is increased in the alveolar compartment of asthmatic patients

Abstract

Increased exhaled nitric oxide (NO) levels in asthma is suggested to be through inducible NO synthase (iNOS). The aim of this study was to investigate the expression of iNOS in BAL cells and tissue from central and peripheral airways and compare it with the exhaled bronchial and alveolar NO levels in asthmatic patients versus a control group.

Methods

Thirty-two asthmatic patients (defined as controlled or uncontrolled according to Asthma Control Test score cut-off: 20) and eight healthy controls were included. Exhaled NO was measured and alveolar concentration and bronchial flux were calculated. iNOS was measured in central and peripheral lung biopsies, as well as BAL cells. BAL macrophages were stimulated in vitro, and iNOS expression and NO production were investigated.

Results

Expression of iNOS was increased in central airway tissue and the alveolar compartment in uncontrolled as compared to controlled asthma and healthy controls. There were no differences, however, in iNOS mRNA levels in total BAL cells in uncontrolled as compared to controlled asthma. BAL cell mRNA levels of iNOS or iNOS expression in central and alveolar tissue did not relate to alveolar NO, nor to bronchial flux of NO. In vitro stimulation with leukotrieneD₄ increased iNOS mRNA levels and NO production in cultured BAL macrophages.

Conclusion

The levels of both bronchial and alveolar iNOS are increased in uncontrolled as compared to controlled asthma. However, levels of iNOS in BAL macrophages were not reflected by alveolar NO. Both central and distal iNOS levels may reflect responsiveness to steroid treatment.

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