Expression of N-acetylglucosamine 6-O-sulfotransferases (GlcNAc6STs)-1 and -4 in human monocytes: GlcNAc6ST-1 is implicated in the generation of the 6-sulfo N-acetyllactosamine/Lewis x epitope on CD44 and is induced by TNF-α

• Published in: Glycobiology (Oxford) 2005-07, Vol.15 (7), p.7C-13C
• Main Authors: Tjew, Sie Lung, Brown, Kelly L., Kannagi, Reiji, Johnson, Pauline
• Format: Article
• Language: English
• Subjects: 2001] for the definition of sulfotransferase nomenclature; 3 fucosyltransferase VII; Amino Sugars - metabolism; Base Sequence; carbohydrate sulfation; Carbohydrate Sulfotransferases; CD44; DNA Primers; Epitopes - metabolism; FCS; fetal calf serum; Fuc-T VII; Gal; Galactosamine; GlcNAc6ST; HEV; high-walled endothelial venules; Humans; Hyaluronan Receptors - metabolism; inflammation; LacNAc; Lewis X Antigen - metabolism; mAb; monoclonal antibody; monocytes; Monocytes - drug effects; Monocytes - enzymology; Monocytes - immunology; Monocytes - metabolism; N-acetylglucosamine 6-O-sulfotransferase (see [Fukuda et al; N-acetyllactosamine; PBM; PBMC; PCR; peripheral blood monocytes; peripheral blood mononuclear cells; polymerase chain reaction; Reverse Transcriptase Polymerase Chain Reaction; RT–PCR; sulfotransferase; Sulfotransferases - metabolism; TNF-α; tumor necrosis factor alpha; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0959-6658; 1460-2423
• DOI: 10.1093/glycob/cwi050

Sulfation at the 6-O position of N-acetylglucosamine (GlcNAc) in the context of sialyl 6-sulfo Lewis x occurs constitutively on specific glycoproteins present on high-walled endothelial venules (HEV) and is important for L-selectin dependent homing of lymphocytes. Here, the proinflammatory cytokine, TNF-α, induced the expression of 6-sulfo N-acetyllactosamine (LacNAc)/Lewis x on human peripheral blood monocytes (PBM). This epitope was detected by monoclonal antibody (mAb) AG107 after neuraminidase treatment suggesting a sialylated epitope, which was present on the cell adhesion molecule, CD44. Treatment of human PBM with TNF-α up-regulated the expression of N-acetylglucosamine 6-O-sulfotransferase-1 (GlcNAc6ST-1) and GlcNAc6ST-4, as determined by reverse transcriptase polymerase chain reaction (RT–PCR). However, only GlcNAc6ST-1 was induced by TNF-α in the human SR91 cell line, which also up-regulated the AG107 epitope. In ECV304 cells, the expression of GlcNAc6ST-4 alone was insufficient to generate the AG107 epitope. However, the transfection of GlcNAc6ST-1 resulted in significant sulfate incorporation into CD44 and generated the 6-sulfo LacNAc/Lewis x epitope on CD44, which was present largely on N‐linked glycans. This demonstrates the induction of GlcNAc6STs in human monocytes in response to TNF-α and implicates GlcNAc6ST-1 in the generation of the 6-sulfo LacNAc/Lewis x epitope on CD44.