title: Structure and immunological characterization of the capsular polysaccharide of a pyrogenic liver abscess caused by Klebsiella pneumoniae: activation of macrophages through Toll-like receptor 4.
abstract: The active components of a primary pyrogenic liver abscess (PLA) Klebsiella pneumoniae in stimulating cytokine expression in macrophages are still unclear. The capsular polysaccharide (CPS) of PLA K. pneumoniae is important in determining clinical manifestations, and we have shown that it consists of repeating units of the trisaccharide (→3)-β-D-Glc-(1→4)-[2,3-(S)-pyruvate]-β-D-GlcA-(1→4)-α-L-Fuc-(1→) and has the unusual feature of extensive pyruvation of glucuronic acid and acetylation of C(2)-OH or C(3)-OH of fucose. We demonstrated that PLA K. pneumoniae CPS induces secretion of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) by macrophages through Toll-like receptor 4 (TLR4) and that this effect was lost when pyruvation and O-acetylation were chemically destroyed. Furthermore, expression of TNF-α and IL-6 in PLA K. pneumoniae CPS-stimulated macrophages was shown to be regulated by the TLR4/ROS/PKC-δ/NF-κB, TLR4/PI3-kinase/AKT/NF-κB, and TLR4/MAPK signaling pathways.
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Feng-Ling
authors.initials: FL
authors.lastname: Yang
authors.forename: Yu-Liang
authors.initials: YL
authors.lastname: Yang
authors.forename: Pei-Chun
authors.initials: PC
authors.lastname: Liao
authors.forename: Ju-Ching
authors.initials: JC
authors.lastname: Chou
authors.forename: Keng-Chang
authors.initials: KC
authors.lastname: Tsai
authors.forename: An-Suei
authors.initials: AS
authors.lastname: Yang
authors.forename: Fuu
authors.initials: F
authors.lastname: Sheu
authors.forename: Tzu-Lung
authors.initials: TL
authors.lastname: Lin
authors.forename: Pei-Fang
authors.initials: PF
authors.lastname: Hsieh
authors.forename: Jin-Town
authors.initials: JT
authors.lastname: Wang
authors.forename: Kuo-Feng
authors.initials: KF
authors.lastname: Hua
authors.forename: Shih-Hsiung
authors.initials: SH
authors.lastname: Wu
mesh_terms: D000038:Abscess; D000818:Animals; D020723:Glucuronic Acid / Q000737:chemistry; D006801:Humans; D007107:Immune System; D015850:Interleukin-6 / Q000378:metabolism; D007711:Klebsiella pneumoniae / Q000378:metabolism*; D008099:Liver / Q000382:microbiology*; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011134:Polysaccharides / Q000737:chemistry*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014312:Trisaccharides / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D011134:Polysaccharides; D051197:Toll-Like Receptor 4; D014312:Trisaccharides; D014409:Tumor Necrosis Factor-alpha; D020723:Glucuronic Acid