Capsular arabinomannans from Mycobacterium avium with morphotype-specific structural differences but identical biological activity.
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.
Wittkowski
Manon
M
Structural Biochemistry, Leibniz-Center for Medicine and Biosciences, Research Center Borstel, D-23845 Borstel, Germany.
Mittelstädt
Jessica
J
Brandau
Sven
S
Reiling
Norbert
N
Lindner
Buko
B
Torrelles
Jordi
J
Brennan
Patrick J
PJ
Holst
Otto
O
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
D003603:Cytotoxins; D008351:Mannans; C012189:arabinomannan