title: The internalization time course of a given lipopolysaccharide chemotype does not correspond to its activation kinetics in monocytes.
abstract: The prerequisites for the initiation of pathophysiological effects of endotoxin (lipopolysaccharide [LPS]) include binding to and possibly internalization by target cells. Monocytes/macrophages are prominent target cells which are activated by LPS to release various pro- and anti-inflammatory mediators. The aim of the present study was to establish a new method to determine the binding and internalization rate of different LPS chemotypes by human monocytes and to correlate these phenomena with biological activity. It was found that membrane-bound LPS disappears within hours from the surface being internalized into the cell. Further, a correlation between the kinetics of internalization and the length of the sugar chain as well as an inverse correlation between the time course of internalization and LPS hydrophobicity was revealed. Comparison of the internalization kinetics of different LPS chemotypes with kinetics of tumor necrosis factor alpha release and kinetics of oxidative burst did not reveal any correlation of these parameters. These findings suggest that cellular internalization of and activation by LPS are mechanisms which are independently regulated.
authors.affiliation: Research Center Borstel, Center for Medicine and Biosciences, Borstel, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Lentschat
authors.forename: V T
authors.initials: VT
authors.lastname: El-Samalouti
authors.forename: J
authors.initials: J
authors.lastname: Schletter
authors.forename: S
authors.initials: S
authors.lastname: Kusumoto
authors.forename: L
authors.initials: L
authors.lastname: Brade
authors.forename: E T
authors.initials: ET
authors.lastname: Rietschel
authors.forename: J
authors.initials: J
authors.lastname: Gerdes
authors.forename: M
authors.initials: M
authors.lastname: Ernst
authors.forename: H
authors.initials: H
authors.lastname: Flad
authors.forename: A J
authors.initials: AJ
authors.lastname: Ulmer
mesh_terms: D001693:Biological Transport, Active; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000737:chemistry / Q000276:immunology; D006017:Glycolipids / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008050:Lipid A / Q000031:analogs & derivatives / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000378:metabolism* / Q000633:toxicity; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects; D012475:Salmonella / Q000737:chemistry / Q000276:immunology; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D006017:Glycolipids; D008050:Lipid A; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C040142:lipid A precursors, bacterial