title: SIGNR1-mediated phagocytosis, but not SIGNR1-mediated endocytosis or cell adhesion, suppresses LPS-induced secretion of IL-6 from murine macrophages.
abstract: C-type lectin receptors (CLRs) serve as phagocytosis receptors for pathogens and also function as adhesion molecules and in the recognition and endocytosis of glycosylated self-antigens. In the present study, we demonstrated that phagocytosis mediated by a mouse mannose-binding CLR, SIGNR1 significantly suppressed the LPS-induced secretion of the specific pro-inflammatory cytokines from the resident peritoneal macrophages and the mouse macrophage-like cells that express SIGNR1 (RAW-SIGNR1). LPS-induced secretion of IL-6 from peritoneal macrophages suppressed in response to uptake of oligomannose-coated liposomes (OMLs), and the suppression was partly inhibited by treatment with an anti-SIGNR1 antibody. LPS-induced secretion of IL-6 from RAW-SIGNR1 cells was also clearly inhibited by treatment of the cells with OMLs >0.4μm in diameter, but treatment with OMLs <0.4μm in diameter did not affect the IL-6 secretion. In contrast, LPS-induced TNF-α secretion from the cells was not affected on treatment of the cells with OMLs. Suppression of the IL-6 secretion was not observed following treatment with oligomannose-containing soluble polymers or when cells were bound to an oligomannose-coated solid phase. Phagocytosis of oligomannose-coated liposomes did not interfere with the transcription of IL-6 mRNA, but did affect IL-6 mRNA stability, leading to suppression of IL-6 secretion. Interestingly, treatment of the cells with Ly290042, a PI3 kinase inhibitor, partly blocked the suppression of LPS-induced secretion of IL-6 by OML. Thus, we conclude that SIGNR1-mediated phagocytosis but not SIGNR1-mediated endocytosis and cell adhesion, suppresses the TLR4-mediated production of specific proinflammatory cytokines via PI3 kinase signaling.
authors.affiliation: Department of Applied Biochemistry, Tokai University, Hiratsuka, Kanagawa 259-1292, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kawauchi
authors.affiliation: Department of Applied Biochemistry, Tokai University, Hiratsuka, Kanagawa 259-1292, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Takagi
authors.affiliation: Department of Applied Biochemistry, Tokai University, Hiratsuka, Kanagawa 259-1292, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Hanafusa
authors.affiliation: Department of Applied Biochemistry, Tokai University, Hiratsuka, Kanagawa 259-1292, Japan.
authors.forename: Mirei
authors.initials: M
authors.lastname: Kono
authors.affiliation: Department of Applied Biochemistry, Tokai University, Hiratsuka, Kanagawa 259-1292, Japan.
authors.forename: Minami
authors.initials: M
authors.lastname: Yamatani
authors.affiliation: Department of Applied Biochemistry, Tokai University, Hiratsuka, Kanagawa 259-1292, Japan. Electronic address: naoyaki@keyaki.cc.u-tokai.ac.jp.
authors.forename: Naoya
authors.initials: N
authors.lastname: Kojima
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology*; D004705:Endocytosis; D006017:Glycolipids / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D037181:Lectins, C-Type / Q000502:physiology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008081:Liposomes / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000502:physiology; D051379:Mice; D010587:Phagocytosis; D000067996:RAW 264.7 Cells; D011956:Receptors, Cell Surface / Q000502:physiology*; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; D000093242:Interleukin-6 Inhibitors
chemical_list: D015815:Cell Adhesion Molecules; D006017:Glycolipids; D015850:Interleukin-6; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D008081:Liposomes; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; D000093242:Interleukin-6 Inhibitors; C493487:Tlr4 protein, mouse; C440499:lipopolysaccharide, Escherichia coli O111 B4
keywords: Cell adhesion; Endocytosis; IL-6; Phagocytosis; SIGNR1