title: Capsular arabinomannans from Mycobacterium avium with morphotype-specific structural differences but identical biological activity.
abstract: The capsules of two colony morphotypes of Mycobacterium avium strain 2151 were investigated, i.e. the virulent smooth-transparent (SmT1) and the nonvirulent smooth-opaque (SmO) types. From both morphotypes we separated a nonacylated arabinomannan (AM) from an acylated polysaccharide fraction by affinity chromatography, of which the AMs were structurally characterized. The AMs from the virulent morphotype, in contrast to that from the nonvirulent form, possessed a larger mannan chain and a shorter arabinan chain. Incubation of murine bone marrow-derived macrophages and human dendritic cells showed that the acylated polysaccharide fractions were potent inducers of tumor necrosis factor-alpha, interleukin-12, and interleukin-10 compared with nonacylated AMs, which led to only a marginal cytokine release. Further in vitro experiments showed that both the acylated polysaccharide fractions and the nonacylated AMs were able to induce in vitro anti-tumor cytotoxicity of human peripheral blood mononuclear cells. Thus, morphotype-specific structural differences in the capsular AMs of M. avium do not correlate with biological activity; however, their acylation is a prerequisite for effective stimulation of murine macrophages and human dendritic cells.
authors: Structural Biochemistry, Leibniz-Center for Medicine and Biosciences, Research Center Borstel, D-23845 Borstel, Germany.
authors: Manon
authors: M
authors: Wittkowski
authors: Jessica
authors: J
authors: Mittelstädt
authors: Sven
authors: S
authors: Brandau
authors: Norbert
authors: N
authors: Reiling
authors: Buko
authors: B
authors: Lindner
authors: Jordi
authors: J
authors: Torrelles
authors: Patrick J
authors: PJ
authors: Brennan
authors: Otto
authors: O
authors: Holst
mesh_terms: D000818:Animals; D002240:Carbohydrate Sequence; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D003603:Cytotoxins / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000382:microbiology*; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000382:microbiology*; D008351:Mannans / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009162:Mycobacterium avium / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D019906:Nuclear Magnetic Resonance, Biomolecular; D013329:Structure-Activity Relationship; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology*; D001749:Urinary Bladder Neoplasms / Q000276:immunology / Q000473:pathology; D014774:Virulence
chemical_list: D003603:Cytotoxins; D008351:Mannans; C012189:arabinomannan