title: Cytokine-induced beta-galactoside alpha-2,6-sialyltransferase in human endothelial cells mediates alpha 2,6-sialylation of adhesion molecules and CD22 ligands.
abstract: Sialic acids decorating blood and cell surface proteins can play important roles in various biological processes. The inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1, as well as bacterial lipopolysaccharide, can activate vascular endothelium, increasing expression of several surface glycoproteins. Here we show that treatment of cultured human endothelial cells (HEC) with TNF-alpha, interleukin-1, or lipopolysaccharide causes increased expression of the enzyme beta-galactoside alpha-2,6-sialytransferase (alpha 2-6STN). TNF-alpha was most effective, inducing a 3.5-fold enhancement of cell-associated sialytransferase activity by 72 h. In addition, activated HEC secreted a large portion of the induced sialyltransferase activity into the medium. Analysis of labeled HEC showed both a relative and an absolute increase of alpha 2,6-linked sialic acid on N-linked oligosaccharides after TNF-alpha stimulation. This coincided with increased expression of endothelial glycoproteins bearing N-linked glycans with alpha 2,6-linked sialic acid detected by the lectin Sambucus nigra agglutinin. The cytokine-inducible endothelial cell adhesion molecules E-selectin, ICAM-1, and VCAM-1 are among these glycoprotein substrates for alpha 2-6STN. These changes also correlated with a substantial increase in binding sites for CD22 beta, a mammalian lectin known to recognize oligosaccharides carrying multiple copies of alpha 2,6-linked sialic acid. Northern analysis revealed increased levels of mRNA encoding alpha 2-6STN. Thus, activation of endothelial cells during inflammatory and immunological processes may induce alpha 2-6STN, which can participate in sialylation of other activation-dependent molecules.
authors.affiliation: Division of Cellular and Molecular Medicine, University of California, San Diego, La Jolla 92093.
authors.forename: K
authors.initials: K
authors.lastname: Hanasaki
authors.forename: A
authors.initials: A
authors.lastname: Varki
authors.forename: I
authors.initials: I
authors.lastname: Stamenkovic
authors.forename: M P
authors.initials: MP
authors.lastname: Bevilacqua
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology*; D004790:Enzyme Induction / Q000187:drug effects; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D037102:Lectins; D008024:Ligands; D019158:N-Acetylneuraminic Acid; D012333:RNA, Messenger / Q000378:metabolism; D051918:Sialic Acid Binding Ig-like Lectin 2; D012794:Sialic Acids / Q000378:metabolism; D012799:Sialyltransferases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
chemical_list: D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C497867:CD22 protein, human; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D007136:Immunoglobulins; D007375:Interleukin-1; D037102:Lectins; D008024:Ligands; D012333:RNA, Messenger; D051918:Sialic Acid Binding Ig-like Lectin 2; D012794:Sialic Acids; D014409:Tumor Necrosis Factor-alpha; D012799:Sialyltransferases; D019158:N-Acetylneuraminic Acid; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase