title: Similar mechanisms of action of defined polysaccharides and lipopolysaccharides: characterization of binding and tumor necrosis factor alpha induction.
abstract: Little has been reported about the effects of different polysaccharides on cytokine production from human monocytes. In this study, we show that several well-defined polysaccharides, including polymers with different sizes of beta 1-4-linked D-mannuronic acid (poly-M, high-M alginate, and M-blocks) and cellulose oxidized in the C-6 position, induced human monocytes to produce tumor necrosis factor alpha (TNF-alpha). Poly-M was the most efficient polysaccharide tested and, on a weight basis, was approximately as efficient as lipopolysaccharide (LPS) from Escherichia coli. TNF-alpha production was shown to depend strongly on the molecular weights of poly-M and high-M alginate, with maximal TNF-alpha production occurring at molecular weights above 50,000 and 200,000, respectively. G-blocks, alpha 1-4-linked L-guluronic acid polymers that did not induce cytokine production from monocytes, reduced the cytokine production induced by the beta 1-4-linked polyuronic acids and LPS. Furthermore, both G-blocks and LPS were found to inhibit the binding of poly-M to monocytes, as measured by flow cytometry. In addition, we found that the binding of LPS to monocytes was inhibited by G-blocks, M-blocks, and poly-M. Our results indicate that beta 1-4-linked polyuronic acids and LPS may stimulate monocytes to produce TNF-alpha by similar mechanisms and may bind to a common receptor.
authors: Institute of Cancer Research, University of Trondheim, Norway.
authors: M
authors: M
authors: Otterlei
authors: A
authors: A
authors: Sundan
authors: G
authors: G
authors: Skjåk-Braek
authors: L
authors: L
authors: Ryan
authors: O
authors: O
authors: Smidsrød
authors: T
authors: T
authors: Espevik
mesh_terms: D001681:Biological Assay; D002240:Carbohydrate Sequence; D004926:Escherichia coli / Q000737:chemistry; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000378:metabolism* / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D011112:Polymyxin B / Q000494:pharmacology; D011135:Polysaccharides, Bacterial / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000737:chemistry; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011135:Polysaccharides, Bacterial; D014409:Tumor Necrosis Factor-alpha; D011112:Polymyxin B