title: Liposome-encapsulated hemoglobin inhibits tumor necrosis factor release from rabbit alveolar macrophages by a posttranscriptional mechanism.
abstract: Macrophages contribute to the systemic inflammatory response that characterizes the sepsis syndrome through the production of inflammatory cytokines such as tumor necrosis factor (TNF). Liposome-encapsulated hemoglobin (LEH), a potential red cell substitute, is cleared by fixed tissue macrophages. In these studies, in vitro incubation of alveolar macrophages with stored LEH was shown to inhibit the expression of TNF induced by endotoxin (lipopolysaccharide, LPS) stimulation. This effect was dependent on LEH dose but independent of the period of exposure to the LEH. Despite inhibition of TNF expression, Northern blot analysis of total cellular RNA from LPS-stimulated macrophages revealed accumulations of TNF-specific transcripts in cells treated with or without LEH. Thus the mechanism of LEH inhibition of TNF expression appears to involve a posttranscriptional event. Although these results suggest a potential advantage of resuscitation with LEH when sepsis complicates hemorrhagic shock, immunomodulation in vivo remains to be defined.
authors: Department of Surgery, University of Washington, Seattle.
authors: L A
authors: LA
authors: Langdale
authors: R V
authors: RV
authors: Maier
authors: L
authors: L
authors: Wilson
authors: T H
authors: TH
authors: Pohlman
authors: J G
authors: JG
authors: Williams
authors: C L
authors: CL
authors: Rice
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D004337:Drug Carriers; D006454:Hemoglobins / Q000494:pharmacology*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008081:Liposomes; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D008854:Microscopy, Electron; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D011817:Rabbits; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D004337:Drug Carriers; D006454:Hemoglobins; D008070:Lipopolysaccharides; D008081:Liposomes; D014409:Tumor Necrosis Factor-alpha