Interaction of primate alveolar macrophages and Legionella pneumophila.
We studied the interaction between Legionella pneumophila, which is principally a pulmonary pathogen, with primate alveolar macrophages (AM), which are the primary pulmonary cellular defense mechanism. For these studies we used L. pneumophila, type I, which were grown in albumin-yeast extract broth, were greater than 80% viable, and were comparable in virulence for guinea pigs to organisms from guinea pig spleen homogenates. For comparison, avirulent agar-passed L. pneumophila, type I, and a strain of Escherichia coli were also used. In the absence of detectable antibody, AM phagocytosed similar numbers of virulent and avirulent Legionella and killed the majority of ingested Legionella in 15-30 min, as determined by two different assays. The virulent and avirulent Legionella appeared to be equally susceptible to the cidal systems of the AM and both were killed more readily than were E. coli under both assay conditions. Phagocytosis of Legionella by AM was associated with a localized respiratory burst, as indicated by nitroblue tetrazolium reduction around ingested organisms. Killing of AM-associated Legionella was inhibited by the hydroxyl radical (OH.) scavenger mannitol (but not by an equiosmolar concentration of sodium sulfate), and by a combination of superoxide dismutase and catalase (but not by either enzyme alone). These findings suggest a contribution by OH., one generated by the metal-catalyzed interaction of superoxide and hydrogen peroxide (Haber-Weiss reaction) in the anti-Legionella activity of AM. The virulent Legionella that survived intracellularly increased in number from 4 X 10(4) at 1 h to 6 X 10(6) at 96 h after infection. In contrast, avirulent Legionella replicated more slowly, increasing in number from 4 X 10(4) to 1 X 10(5) over the same period. Replication of virulent Legionella destroyed the AM monolayers by 120 h, whereas monolayers containing avirulent organisms remained intact. Thus, virulence of Legionella appears not to correlate with its ability to survive early killing by AM, but rather with the ability of the small fraction of surviving organisms to replicate within these cells.
D000818:Animals; D002250:Carbon Radioisotopes; D002374:Catalase / Q000633:toxicity; D004926:Escherichia coli / Q000502:physiology; D007700:Kinetics; D007875:Legionella / Q000472:pathogenicity / Q000502:physiology*; D008254:Macaca nemestrina; D008264:Macrophages / Q000382:microbiology / Q000502:physiology* / Q000648:ultrastructure; D008854:Microscopy, Electron; D010587:Phagocytosis; D011650:Pulmonary Alveoli / Q000382:microbiology; D013462:Sulfur Radioisotopes; D013482:Superoxide Dismutase / Q000633:toxicity; D014774:Virulence
D002250:Carbon Radioisotopes; D013462:Sulfur Radioisotopes; D002374:Catalase; D013482:Superoxide Dismutase