title: The involvement of CD14 in stimulation of cytokine production by uronic acid polymers.
abstract: In this study the molecular mechanisms behind the stimulatory activities of the uronic acid polymers poly mannuronic acid (poly M), high M alginate and oxidized cellulose (C60XY) were investigated and compared with lipopolysaccharide (LPS). The cytokine-inducing abilities of the uronic acid polymers and LPS were examined on CD14-positive human monocytes and CD14-negative U373 astrocytoma cells. It was found that LPS induced monocytes and U373 cells to produce tumor necrosis factor (TNF) and interleukin(IL)-6, respectively, by different mechanisms. The poly uronic acids induced monocytes to produce TNF, but with 100-1000 times less potency compared to LPS. On U373 cells, LPS at concentrations > or = 32 ng/ml resulted in a dose-related IL-6 production, whereas the poly uronic acids had negligible effects even at 1 mg/ml. The binding data demonstrate that only the CD14-positive monocytes in the peripheral blood mononuclear cells population bound poly M. Furthermore, poly M was found to bind to CD14 in the presence of serum. Antibodies against CD14 also inhibited the TNF-inducing activity of the three uronic acid polymers tested. In conclusion, these results demonstrate that uronic acid polymers induce TNF production through mechanisms which involve CD14.
authors.affiliation: Institute of Cancer Research, University of Trondheim, Norway.
authors.forename: T
authors.initials: T
authors.lastname: Espevik
authors.forename: M
authors.initials: M
authors.lastname: Otterlei
authors.forename: G
authors.initials: G
authors.lastname: Skjåk-Braek
authors.forename: L
authors.initials: L
authors.lastname: Ryan
authors.forename: S D
authors.initials: SD
authors.lastname: Wright
authors.forename: A
authors.initials: A
authors.lastname: Sundan
mesh_terms: D000464:Alginates / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D005965:Glucuronates / Q000494:pharmacology; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D000464:Alginates; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D005965:Glucuronates; D006603:Hexuronic Acids; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D020723:Glucuronic Acid