Increased arginase activity in cystic fibrosis airways.
BACKGROUND
Airway nitric oxide concentrations are reduced in cystic fibrosis (CF). Arginases compete for L-arginine, the substrate of nitric oxide synthesis.


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


METHODS
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.
Grasemann
Hartmut
H
Children's Hospital, University of Duisburg-Essen, Essen, Germany. hartmut.grasemann@sickkids.ca
Schwiertz
Raphael
R
Matthiesen
Sonja
S
Racké
Kurt
K
Ratjen
Felix
F
D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D001119:Arginase / Q000378:metabolism*; D001944:Breath Tests; D016022:Case-Control Studies; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D012129:Respiratory Function Tests; D013183:Sputum / Q000201:enzymology*
D000900:Anti-Bacterial Agents; D009569:Nitric Oxide; D001119:Arginase