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J. Biol. Chem., Vol. 282, Issue 26, 19103-19112, June 29, 2007

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Capsular Arabinomannans from Mycobacterium avium with Morphotype-specific Structural Differences but Identical Biological Activity^*

Manon Wittkowski, Jessica Mittelstädt, Sven Brandau¹, Norbert Reiling^¶, Buko Lindner^||, Jordi Torrelles^**23, Patrick J. Brennan^**3, and Otto Holst⁴

From the Structural Biochemistry, Immunotherapy, ^¶Molecular Infection Biology, and ^||Biophysics, Leibniz-Center for Medicine and Biosciences, Research Center Borstel, D-23845 Borstel, Germany and the ^**Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523-1682

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-, 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.

Received for publication, December 18, 2006 , and in revised form, April 10, 2007.

^* This work was supported in part by Deutsche Forschungsgemeinschaft Grant SFB 470 B1 (to O. H.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1-S5 and Tables S1-S5.

¹ Present address: Dept. of Otorhinolaryngology, Head and Neck Surgery, University Hospital Essen, D-45122 Essen, Germany.

² Present address: Dept. of Medicine, Division of Infectious Diseases, and Dept. of Molecular Virology, Immunology, and Medical Genetics, Center for Microbial Interface Biology, Ohio State University, Columbus, OH 43210.

³ Supported by Grant AI 018357 from NIAID, National Institutes of Health.

⁴ To whom correspondence should be addressed. Tel.: 49-4537-188472; Fax: 49-4537-188745; E-mail: oholst{at}fz-borstel.de.

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