title: Hyperoxia amplifies TNF-alpha production in LPS-stimulated human alveolar macrophages.
abstract: Human alveolar macrophages (AM) produce a number of inflammatory mediators including tumor necrosis factor (TNF). TNF-alpha has been implicated in several forms of lung injury including that associated with oxygen toxicity. To investigate whether oxygen could induce or augment the release of TNF from AM, we acquired AM from nonsmoking volunteers and determined TNF release after in vitro hyperoxia. Although TNF release was not induced by oxygen exposure alone, if lipopolysaccharide (LPS) stimulation occurred simultaneously, there was significant augmentation by 60 and 95% oxygen over LPS-stimulated AM exposed to 21% oxygen. This increase was paralleled by a significant increase of interleukin (IL)-1 beta. Dimethylthiourea (DMTU), a hydroxyl radical scavenger, inhibited this release. The increase in TNF extracellular concentrations induced by hyperoxia was not associated with significant increases in intracellular concentration or detectable mRNA over LPS-stimulated AM exposed to 21% oxygen. We hypothesize that hyperoxia exposure may alter the LPS-stimulated AM cytoplasmic milieu, thus further enhancing TNF-alpha production by a post-transcriptional mechanism.
authors.affiliation: Department of Medicine, University of Kansas Medical Center, Kansas City 66160-7381.
authors.forename: A R
authors.initials: AR
authors.lastname: O'Brien-Ladner
authors.forename: M E
authors.initials: ME
authors.lastname: Nelson
authors.forename: B D
authors.initials: BD
authors.lastname: Cowley
authors.forename: K
authors.initials: K
authors.lastname: Bailey
authors.forename: L J
authors.initials: LJ
authors.lastname: Wesselius
mesh_terms: D001992:Bronchoalveolar Lavage Fluid; D002470:Cell Survival; D002478:Cells, Cultured; D006801:Humans; D018496:Hyperoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D007770:L-Lactate Dehydrogenase