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Increased Arginase Activity in Cystic Fibrosis Airways

Children's Hospital, University of Duisburg-Essen, Essen; and Institute for Pharmacology and Toxicology, University of Bonn, Bonn, Germany

Correspondence and requests for reprints should be addressed to Hartmut Grasemann, M.D., The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, ON M5G 1X8, Canada. E-mail: hartmut.grasemann{at}sickkids.ca

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.

Key Words: inflammatory marker • nitric oxide • pulmonary function

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