Cytokine-induced beta-galactoside alpha-2,6-sialyltransferase in human endothelial cells mediates alpha 2,6-sialylation of adhesion molecules and CD22 ligands

J Biol Chem. 1994 Apr 8;269(14):10637-43.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD / metabolism*
  • Antigens, Differentiation, B-Lymphocyte / metabolism*
  • Cell Adhesion Molecules / metabolism*
  • Cells, Cultured
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / enzymology*
  • Enzyme Induction / drug effects
  • Glycoproteins / metabolism
  • Humans
  • Immunoglobulins / metabolism
  • Interleukin-1 / pharmacology*
  • Lectins*
  • Ligands
  • N-Acetylneuraminic Acid
  • RNA, Messenger / metabolism
  • Sialic Acid Binding Ig-like Lectin 2
  • Sialic Acids / metabolism
  • Sialyltransferases / biosynthesis*
  • Sialyltransferases / genetics
  • Sialyltransferases / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*
  • beta-D-Galactoside alpha 2-6-Sialyltransferase


  • Antigens, CD
  • Antigens, Differentiation, B-Lymphocyte
  • CD22 protein, human
  • Cell Adhesion Molecules
  • Glycoproteins
  • Immunoglobulins
  • Interleukin-1
  • Lectins
  • Ligands
  • RNA, Messenger
  • Sialic Acid Binding Ig-like Lectin 2
  • Sialic Acids
  • Tumor Necrosis Factor-alpha
  • Sialyltransferases
  • N-Acetylneuraminic Acid
  • beta-D-Galactoside alpha 2-6-Sialyltransferase