DIFFERENTIAL NITRIC-OXIDE (NO) PRODUCTION BY MACROPHAGES FROM MICE AND GUINEA-PIGS INFECTED WITH VIRULENT AND AVIRULENT LEGIONELLA-PNEUMOPHILA SEROGROUP-1

L-arginine-dependent reactive nitrogen intermediates have been identif ied as macrophage cytotoxic effector molecules against intracellular p athogens. To determine its role, ex vivo production of NO by peritonea l macrophages of C3H/HeN mice and Dunkin-Hartley guinea pigs infected intraperitoneally with a virulent and isogenic avirulent Legionella pn eumophila serogroup 1 strain was compared with bacterial clearance fro m the lungs. While the virulent strain was cleared from mice lungs, th e guinea pigs died within 96 h. In vivo infection with both strains re sulted in the production of NO by mouse peritoneal macrophages ex vivo . In contrast, guinea pig macrophages did not produce detectable NO. I n addition, infection by the avirulent strain led to the production of significantly more NO by mouse macrophages than the virulent parent s train, irrespective of stimulation with lipopolysaccharide (LPS) and/o r interferon-gamma (IFN-gamma). These results suggest that resistance to Leg. pneumophila infection may depend on the production of NO by ho st macrophages.