title: Global analysis of glycoproteins identifies markers of endotoxin tolerant monocytes and GPR84 as a modulator of TNFα expression.
abstract: Exposure of human monocytes to lipopolysaccharide (LPS) induces a temporary insensitivity to subsequent LPS challenges, a cellular state called endotoxin tolerance. In this study, we investigated the LPS-induced global glycoprotein expression changes of tolerant human monocytes and THP-1 cells to identify markers and glycoprotein targets capable to modulate the immunosuppressive state. Using hydrazide chemistry and LC-MS/MS analysis, we analyzed glycoprotein expression changes during a 48 h LPS time course. The cellular snapshots at different time points identified 1491 glycoproteins expressed by monocytes and THP-1 cells. Label-free quantitative analysis revealed transient or long-lasting LPS-induced expression changes of secreted or membrane-anchored glycoproteins derived from intracellular membrane coated organelles or from the plasma membrane. Monocytes and THP-1 cells demonstrated marked differences in glycoproteins differentially expressed in the tolerant state. Among the shared differentially expressed glycoproteins G protein-coupled receptor 84 (GPR84) was identified as being capable of modulating pro-inflammatory TNFα mRNA expression in the tolerant cell state when activated with its ligand Decanoic acid.
authors.affiliation: Septomics Research Center, Jena University Hospital, Jena, Germany.|Jena University Hospital, Integrated Research and Treatment Center - Center for Sepsis Control and Care (CSCC), Jena, Germany.
authors.forename: Mario M
authors.identifier: http://orcid.org/0000-0002-1898-5691
authors.initials: MM
authors.lastname: Müller
authors.affiliation: Septomics Research Center, Jena University Hospital, Jena, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Lehmann
authors.affiliation: Septomics Research Center, Jena University Hospital, Jena, Germany.
authors.forename: Tilman E
authors.initials: TE
authors.lastname: Klassert
authors.affiliation: Septomics Research Center, Jena University Hospital, Jena, Germany.
authors.forename: Stella
authors.initials: S
authors.lastname: Reifenstein
authors.affiliation: Septomics Research Center, Jena University Hospital, Jena, Germany.|Leibnitz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institut, Jena, Germany.
authors.forename: Theresia
authors.initials: T
authors.lastname: Conrad
authors.affiliation: Septomics Research Center, Jena University Hospital, Jena, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Moore
authors.affiliation: Septomics Research Center, Jena University Hospital, Jena, Germany.|Leibnitz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institut, Jena, Germany.
authors.forename: Anna
authors.identifier: http://orcid.org/0000-0001-5757-7570
authors.initials: A
authors.lastname: Kuhn
authors.affiliation: Jena University Hospital, Integrated Research and Treatment Center - Center for Sepsis Control and Care (CSCC), Jena, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Behnert
authors.affiliation: Leibnitz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institut, Jena, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Guthke
authors.affiliation: BioControl Jena GmbH, Jena, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Driesch
authors.affiliation: Septomics Research Center, Jena University Hospital, Jena, Germany. Hortense.Slevogt@med.uni-jena.de.
authors.forename: Hortense
authors.initials: H
authors.lastname: Slevogt
mesh_terms: D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003652:Decanoic Acids / Q000494:pharmacology; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D020543:Proteome; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D003652:Decanoic Acids; C431700:GPR84 protein, human; D006023:Glycoproteins; D008070:Lipopolysaccharides; D020543:Proteome; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha; C031071:decanoic acid