Guinea pig ozone-induced airway hyperreactivity is associated with increased N-acetyl-β-D-glucosaminidase activity in bronchoalveolar lavage fluid

Abstract

High level ozone exposure is known to cause acute, neutrophil-independent airway hyperreactivity in the guinea pig. The precise biochemical mechanisms involved remain unclear. Because of its potential pathophysiologic importance, we examined whether a lysosomal hydrolase, N-acetyl-beta-D-glucosaminidase (NAGA) was released from the airways in vivo and from bronchoalveolar cells, specifically macrophages. Muscarinic reactivity was determined by measuring specific airway resistance (sRaw) in response to increasing doses of aerosolized acetylcholine in guinea pigs that were either exposed to air or to ozone (3.0 ppm, 2 h). The ozone-exposed animals showed substantial muscarinic hyperreactivity 30 min after exposure. In addition, both total and percent released NAGA in bronchoalveolar lavage fluid obtained immediately after reactivity testing were significantly greater in the ozone-exposed group. It was also found that substantially more NAGA was released from mixed bronchoalveolar lavage cells in response to 20 microM A23187. Moreover, bronchoalveolar macrophages of ozone-exposed animals secreted more NAGA upon stimulation in vitro by either 20 microM A23187 or 200 micrograms/ml opsonized zymosan. We conclude that ozone-induced airway hyperreactivity in guinea pigs is associated with the presence of increased NAGA activity in bronchoalveolar fluid. Our data suggest that bronchoalveolar macrophages may, at least in part, be responsible for release of this enzyme into the airways after ozone exposure.