LUNG PHAGOCYTE BACTERICIDAL FUNCTION IN STRAINS OF MICE RESISTANT ANDSUSCEPTIBLE TO PSEUDOMONAS-AERUGINOSA

The host response to Pseudomonas aeruginosa lung infection varies amon g inbred mouse strains. Mice of the BALB/c strain are resistant to P. aeruginosa lung infection, whereas mice of the DBA/2 strain are suscep tible. This phenotypic variation correlates with a difference in the m agnitude of the inflammatory response induced early following infectio n. In order to determine whether the ability of lung phagocytic cells to kill P. aeruginosa plays a role in the host response to the infecti on, we measured the in vitro bactericidal activity of resident and inf lammatory alveolar and interstitial macrophages, using a temperature-s ensitive mutant of P. aeruginosa. Lung macrophages obtained from resis tant and susceptible animals displayed similar bactericidal activities , suggesting that the ability of phagocytes to kill P. aeruginosa does not play a crucial role in the outcome of infection. The bactericidal activity of lung phagocytes was also assessed in vivo following endob ronchial infection with the temperature-sensitive mutant of P. aerugin osa, Resistant mice shelved a rapid influx of polymorphonuclear leukoc ytes (PMNs) to the bronchoalveolar space which was shortly followed by an efficient clearance of the bacteria. Susceptible mice had a delay in both the inflammatory response to P. aeruginosa and the initiation of bacterial clearance. Susceptible mice have been shown to have a def ect in tumor necrosis factor alpha production when infected intratrach eally with P. aeruginosa, Intratracheal instillation of tumor necrosis factor alpha to susceptible mice at the time of infection significant ly improved the recruitment of PMNs to the site of infection without a ffecting the process of bacterial clearance. Overall, these results su ggest that both recruitment of a high number of PMNs to the lungs and an efficient activation process of the phagocytes are crucial for the prompt clearance of P. aeruginosa.