Legionella pneumophila growth restriction and cytokine production by murine macrophages activated by a novel Pseudomonas lipid A.
Peritoneal exudate macrophages from A/J mice activated by purified lipid A preparations from Pseudomonas vesicularis, which contain 2,3-diamino-2,3-dideoxy-D-glucose disaccharide phosphomonoester as the lipid A backbone, restricted the growth of Legionella pneumophila, an intracellular opportunistic bacteria which readily grows in otherwise permissive macrophages from susceptible A/J mice and induced production of the proinflammatory cytokines interleukin 1 and tumor necrosis factor alpha. Activation of the macrophages was similar to that which occurred after stimulation with more conventional lipid A from other bacteria such as salmonellae. A purified fraction A3 preparation from the Pseudomonas lipid A, which lacked only 1 mol of amide-linked fatty acid, in comparison with another fraction (A2), which contained the fatty acid, also markedly activated the usually permissive macrophages from susceptible A/J mice to resist growth of the legionellae. The fraction A3 also induced both interleukin and tumor necrosis factor alpha. These results show that this novel lipid A from P. vesicularis can activate macrophages to resist infection with an opportunistic bacterium in a manner similar to that induced by conventional enterobacterial lipid A and that the hydrophobic portion of this Pseudomonas molecule may have an important role in activation of macrophages.
Arata
S
S
Department of Microbial Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Kasai
N
N
Klein
T W
TW
Friedman
H
H
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D004731:Endotoxins / Q000494:pharmacology; D005944:Glucosamine / Q000031:analogs & derivatives / Q000737:chemistry; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis; D016952:Legionella pneumophila / Q000254:growth & development / Q000276:immunology*; D008050:Lipid A / Q000737:chemistry / Q000494:pharmacology*; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008805:Mice, Inbred A; D015394:Molecular Structure; D011549:Pseudomonas; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D004731:Endotoxins; D007375:Interleukin-1; D008050:Lipid A; D014409:Tumor Necrosis Factor-alpha; C040138:2,3-diamino-2,3-dideoxyglucose; D005944:Glucosamine