title: Anti-inflammatory activity of low molecular weight polysialic acid on human macrophages.
abstract: Oligosialic and polysialic acid (oligoSia and polySia) of the glycocalyx of neural and immune cells are linear chains, in which the sialic acid monomers are α2.8-glycosidically linked. Sialic acid-binding immunoglobulin-like lectin-11 (SIGLEC-11) is a primate-lineage specific receptor of human tissue macrophages and microglia that binds to α2.8-linked oligoSia. Here, we show that soluble low molecular weight polySia with an average degree of polymerization 20 (avDP20) interacts with SIGLEC-11 and acts anti-inflammatory on human THP1 macrophages involving the SIGLEC-11 receptor. Soluble polySia avDP20 inhibited the lipopolysaccharide (LPS)-induced gene transcription and protein expression of tumor necrosis factor-α (Tumor Necrosis Factor Superfamily Member 2, TNFSF2). In addition, polySia avDP20 neutralized the LPS-triggered increase in macrophage phagocytosis, but did not affect basal phagocytosis or endocytosis. Moreover, polySia avDP20 prevented the oxidative burst of human macrophages triggered by neural debris or fibrillary amyloid-β1-42. In a human macrophage-neuron co-culture system, polySia avDP20 also reduced loss of neurites triggered by fibrillary amyloid-β1-42. Thus, treatment with polySia avDP20 might be a new anti-inflammatory therapeutic strategy that also prevents the oxidative burst of macrophages.
authors.affiliation: Institute of Reconstructive Neurobiology, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany.
authors.forename: Anahita
authors.initials: A
authors.lastname: Shahraz
authors.affiliation: Institute of Reconstructive Neurobiology, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Kopatz
authors.affiliation: Institute of Reconstructive Neurobiology, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany.
authors.forename: Rene
authors.initials: R
authors.lastname: Mathy
authors.affiliation: Institute of Biochemistry and Molecular Biology, University Hospital Bonn, University Bonn, Nussallee 11, 53115 Bonn, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Kappler
authors.affiliation: Institute of Biochemistry and Molecular Biology, University Hospital Bonn, University Bonn, Nussallee 11, 53115 Bonn, Germany.
authors.forename: Dominic
authors.initials: D
authors.lastname: Winter
authors.affiliation: Institute of Reconstructive Neurobiology, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany.
authors.forename: Shoba
authors.initials: S
authors.lastname: Kapoor
authors.affiliation: Institute of Reconstructive Neurobiology, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany.
authors.forename: Vlad
authors.initials: V
authors.lastname: Schütza
authors.affiliation: Institute of Technical Chemistry, Leibnitz University Hannover, Callinstraße 5, 30167 Hannover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Scheper
authors.affiliation: Institute of Biochemistry and Molecular Biology, University Hospital Bonn, University Bonn, Nussallee 11, 53115 Bonn, Germany.
authors.forename: Volkmar
authors.initials: V
authors.lastname: Gieselmann
authors.affiliation: Institute of Reconstructive Neurobiology, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Neumann
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D037102:Lectins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008863:Microspheres; D008970:Molecular Weight; D018696:Neuroprotective Agents / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D058105:Polymerization; D016897:Respiratory Burst / Q000187:drug effects; D012794:Sialic Acids / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D037102:Lectins; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D018696:Neuroprotective Agents; C464442:SIGLEC11 protein, human; D012794:Sialic Acids; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C021319:polysialic acid