Increased Arginase Activity in Cystic Fibrosis Airways

Rationale: Airway nitric oxide concentrations are reduced in cystic fibrosis (CF). Arginases compete for L-arginine, the substrate of nitric oxide synthesis.

Objectives: We hypothesized that increased arginase activity may be one factor contributing to nitric oxide deficiency in CF.

Measurements: We therefore studied sputum arginase activity, exhaled nitric oxide, and pulmonary function in patients with cystic fibrosis.

Results: Mean (+/- SEM) sputum arginase activity was significantly higher in patients admitted for pulmonary exacerbation compared with patients with stable disease (1.032 +/- 0.148 vs. 0.370 +/- 0.091 U/mg protein, p = 0.004). Fourteen days of intravenous antibiotic treatment resulted in significantly decreased sputum arginase activity in all patients (p = 0.0002). However, arginase activity was still significantly (p = 0.0001) higher in CF sputum after treatment for exacerbation compared with induced sputum from healthy control subjects (0.026 +/- 0.006 U/mg protein). Negative correlations were found for sputum arginase activity at admission with FEV1 (r = -0.41, p = 0.01), as well as changes in arginase activity with percent change in FEV1 during antibiotic therapy (r = -0.4, p < 0.01) in CF. Exhaled nitric oxide in CF was positively correlated to FEV1 (r = 0.34, p = 0.007), and in patients admitted for pulmonary exacerbation negatively correlated to sputum arginase activity (r = -0.45, p = 0.03).

Conclusions: These data suggest that increased sputum arginase activity contributes to nitric oxide deficiency in CF lung disease and may be relevant in the pathogenesis of CF airway disease.