Modulation of pulmonary defense mechanisms by acute exposures to nitrogen dioxide.
The effect of acute exposures to NO2 on the antibacterial defenses of the murine lung was assessed following inhalation challenges with Staphylococcus aureus, Proteus mirabilis, and Pasteurella pneumotropica. Animals were challenged with the bacteria and exposed for 4 hr to increasing concentrations of NO2 after which pulmonary bactericidal activity was quantitated. With S. aureus pulmonary antibacterial defenses were suppressed at NO2 levels of 4.0 ppm and greater. Exposure to 10.0 ppm enhanced the intrapulmonary killing of P. mirabilis which correlated with an increase in the phagocytic cell populations lavaged from the lungs; at 20.0 ppm bactericidal activity against P. mirabilis was impaired. Pulmonary antibacterial defenses against P. pneumotropica were impaired at 10.0 ppm which correlated with a decrease in the retrieved phagocytic lung cell population. Reversing the order of treatment (ie., NO2 exposure prior to bacterial challenge) raised the threshold concentration for NO2-induced impairment of intrapulmonary bacterial killing. With S. aureus the effect was not observed at 5.0 ppm but at 10.0 ppm and with P. mirabilis not at 20.0 ppm but at 30.0 ppm intrapulmonary killing was enhanced. Exposures up to 20.0 ppm of NO2 did not effect the physical translocation mechanisms of the lung as quantitated by declines in pulmonary radiotracer activity following aerogenic challenge with 32P-labeled staphylococci. These studies demonstrate that NO2 modulates pulmonary antibacterial defenses and points to the importance of the challenge organism and the exposure protocol in establishing a threshold dose for the adverse effect.
D000818:Animals; D001419:Bacteria / Q000276:immunology; D001980:Bronchi / Q000166:cytology; D001985:Bronchial Provocation Tests; D002452:Cell Count / Q000187:drug effects; D005260:Female; D008168:Lung / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D009585:Nitrogen Dioxide / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000166:cytology; D007507:Therapeutic Irrigation; D013997:Time Factors
D009585:Nitrogen Dioxide