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Identification of an N-acetylglucosamine-6-O-sulfotransferase activity specific to lymphoid tissue: an enzyme with a possible role in lymphocyte homing

Identification of an N-acetylglucosamine-6-O-sulfotransferase activity specific to lymphoid tissue: an enzyme with a possible role in lymphocyte homin

Identification of an N-acetylglucosamine-6-O-sulfotransferase activity specific to lymphoid tissue: an enzyme with a possible role in lymphocyte homing   (Citations: 13)
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Background: The leukocyte adhesion molecule L-selectin participates in the initial attachment of blood-borne lymphocytes to high endothelial venules (HEVs) during lymphocyte homing to secondary lymphoid organs, and contributes to leukocyte adhesion and extravasation in HEV-like vessels at sites of chronic inflammation. The L-selectin ligands on lymph node HEVs are mucin-like glycoproteins adorned with the unusual sulfated carbohydrate epitope, 6-sulfo sialyl Lewis x. Sulfation of this epitope on the N-acetylglucosamine (GICNAc) residue confers high-avidity L-selectin binding, and is thought to be restricted in the vasculature to sites of sustained lymphocyte recruitment. The GIcNAc-6-Osulfotransferase that installs the sulfate ester may be a key modulator of lymphocyte recruitement to secondary lymphoid organs and sites of chronic inflammation and is therefore a potential target for anti-inflammatory therapy.Results: A GIcNAc-6-O-sulfotransferase activity was identified within porcine lymph nodes and characterized using a rapid, sensitive, and quantitative assay. We synthesized two unnatural oligosaccharide substrates, GIcNAcβ1 →6Galα-R and Galβ1→4GIcNAcβ1 →6Galα-R, that incorporate structural motifs from the native L-selectin ligands into an unnatural C-glycosyl hydrocarbon scaffold. The sulfotransferase incorporated greater than tenfold more sulfate into the disaccharide than the trisaccharide, indicating a requirement for a terminal GlcNAc. Activity across tissues was highly restricted to the HEVs within peripheral lymph node.Conclusions: The restricted expression of the GIcNAc-6-O-sulfotransferase activity to lymph node HEVs strongly suggests a role in the biosynthesis of L-selectin ligands. In addition, similar sulfated epitopes are known to be expressed on HEV-like vessels of chronically inflamed tissues, indicating that this sulfotransferase may also contribute to inflammatory lymphocyte recruitment. We identified a concise disaccharide motif, GIcNAcβ1 →6-Galα-R, that preserved both recognition and specificity determinants for the GIcNAc-6-O-sulfotransferase. The absence of activity on the trisaccharide Galβ1→4-GIcNAcβ1 →6-Galα-R indicates a requirement for a substrate with a terminal GIcNAc residue, suggesting that sulfation precedes further biosynthetic assembly of L-selectin ligands.
Journal: Chemistry & Biology - CHEM BIOL , vol. 5, no. 8, pp. 447-460, 1998
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    • ...Sulfotransferases involved in the sulfation of oligosaccharides have been characterized (Hooper et al., 1995; Spiro et al., 1996; Chandrasekaran et al., 1997; Degroote et al. ,1 997; Bowman et al., 1988; Spiro and Bhoyroo, 1998) and some sulfotransferases were cloned (Bakker et al., 1997; Ong et al., 1998; Uchimura et al., 1998; Bistrup et al. ,1 999)...

    Takayoshi Toriiet al. Sulfation of sialyl N-acetyllactosamine oligosaccharides and fetuin ol...

    • ...The GlcNAc:→6SulT enzymatic activities in rat stomach (Carter et al., 1988) rat corpus (Goso and Hotta, 1993), rat liver (Spiro et al. ,1 996), human respiratory mucosa (Degroote et al., 1997), and porcine lymph nodes (Bowman et al., 1998) have been characterized, and recently the genes for three types of GlcNAc:→6SulT have been cloned (Uchimura et al., 1998a,b; Bistrup et al., 1999; Hiraoka et al., 1999; Lee et al., 1999)...
    • ...GlcNAc:→6SulTs activities have been identified and characterized in rat stomach (Carter et al., 1988), rat corpus (Goso and Hotta, 1993), rat liver (Spiro et al. ,1 996), human respiratory mucosa (Degroote et al., 1997), and porcine lymph nodes (Bowman et al., 1998)...

    Akira Sekoet al. Biochemical differences between two types of N-acetylglucosamine:->6su...

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