Exposure to nitric acid stimulates human alveolar macrophage function but does not cause inflammation or changes in lung function

Nitric acid (HNO3) is common component of air pollution possibly associated with increased risk for airway infection, airway injury, and inflammation. To experimentally address this question, we exposed 9 healthy nonsmoking volunteers once to HNO3 vapor (200 mu g/m(3), 0.08 ppm), and once to filtered air, for 2 h with 100 min of moderate intermittent exercise (ventilation rate 39 L/min). Pulmonary functions (spirometry and airway resistance) were measured, as were subjective symptoms of response. Bronchoalveolar lavage (BAL) was performed 18 h after exposure, and cells and fluid were analyzed for indicators of airway injury and inflammation. As a measure of host defense capability against infectious disease, alveolar macrophages (AM) were tested for phagocytosis of Candida albicans and for susceptibility to infection with respiratory syncytial virus (RSV). Exposure to HNO3 did not change pulmonary function nor measures of symptoms. Compared to air-exposed BAL, there was no significant increase in protein, lactate dehydrogenase, fibronectin, prostaglandin E(2), leukotriene B-4, C3a, alpha-l-antitrypsin, or interleukin 6 in the HNO3-exposed BAL, nor was there an increase in polymorphonuclear neutrophils (PMN). This indicates that acute exposure to environmentally high levels of HNO3 vapor that can be encountered in ambient air does not cause permeability changes, cell damage, or inflammation in the lung. On the other hand, there was a significant increase in the phagocytic activity of AM after HNO3 exposure. Phagocytosis of both unopsonized and serum-opsonized C. albicans was increased by 85% and 24% respectively. Furthermore, HNO3-exposed AM showed increased resistance to infection with RSV and released 72% less RSV than AM from subjects exposed to filtered air. Superoxide anion production in response to adherence was undetectable in the HNO3-exposed AM but was produced by the air-exposed cells. Thus, these results suggest that HNO3 at 0.08 ppm does not cause acute injury in the lung. instead host defense functions of AM such as phagocytic and antiviral activities are stimulated after HNO3 inhalation.