Induction of inducible nitric oxide synthase by lipopolysaccharide/interferon gamma and sepsis down-regulates 5-lipoxygenase metabolism in murine alveolar macrophages.
Pretreatment with lipopolysaccharide (LPS) suppresses rat alveolar macrophage leukotriene synthesis in a nitric oxide (NO)-dependent mechanism. The authors examined the effect of NO on alveolar macrophage leukotriene synthesis following in vitro and in vivo models of sepsis. Treatment of alveolar macrophages from inducible NO synthase (iNOS) wild-type but not knock-out mice with LPS inhibited leukotriene synthesis. iNOS was induced early in alveolar macrophages from cecal ligation and puncture rats and mice compared to sham animals with associated reduced leukotriene synthesis. iNOS knock-out mice were protected from the decrease in alveolar macrophage 5-lipoxygenase metabolism. iNOS regulates alveolar macrophage 5-lipoxygenase metabolism following endotoxin exposure.
Coffey
Michael
M
Division of Pulmonary and Critical Care Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0642, USA. coffeym@umich.edu
Phare
Susan
S
Peters-Golden
Marc
M
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D002432:Cecum; D015536:Down-Regulation; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D007371:Interferon-gamma / Q000494:pharmacology*; D015289:Leukotrienes / Q000096:biosynthesis; D008026:Ligation; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000276:immunology / Q000503:physiopathology*; D013047:Specific Pathogen-Free Organisms; D014951:Wounds, Stab
D015289:Leukotrienes; D008070:Lipopolysaccharides; D007371:Interferon-gamma; D001094:Arachidonate 5-Lipoxygenase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat