Arginase Expression in Airways of Mice Exposed to Ovalbumin

摘要

Arginase gene expression in the lung has been linked to asthma in humans and in the mouse model of ovalbumin-induced airway inflammation. We tested the hypotheses that the content of the arginase I and/or arginase II enzymes would be increased in airways of mice exposed to ovalbumin and that the average concentrations of arginine in the conducting airways of mice exposed to ovalbumin would be lower during the peak inflammatory response. Methods: Micro-dissected airway preparations were prepared from sensitized mice exposed to ovalbumin aerosol for 1 to 4 weeks, and arginase I and arginase II were measured by Western blot analysis. Physiological and biochemical responses—inflammation, airway hyperreactivity, Fe NO, and airway arginine concentration of C57BL mice—were compared with the responses of an NOS2~-1-strain to address the role of NOS2 in the observed responses to ovalbumin. Results: Both arginase I and II were constitutively expressed in the airways of normal C57BL mice. Arginase I, which was expressed at relatively low levels in normal C57BL mice, was up-regulated by approximately eightfold in the airways of C57BL mice exposed to ovalbumin, while there were no significant changes in the levels of arginase II. There were about 40- and 4-fold increases in arginase I and II, respectively, upon exposure of the NOS2~-/-mice to ovalbumin. The concentration of arginine found in isolated airways from C57BL mice exposed to filtered air or ovalbumin for 0, 1, 2, or 4 weeks was the same, and was not different from the corresponding values for the NOS2~'~ strain. This differs from our previous findings in Balb/c mice at 2 weeks. Conclusions: We conclude that during the acute inflammatory response of C57BL and NOS2~-/- mice to ovalbumin, the contents of arginase I and II increase in the airways of the mice; however, there was no significant decrease in the concentration of arginine in these same airways at the time points sampled.