Human myeloid alpha 3-fucosyltransferase is involved in the expression of
the sialyl-Lewis(x) determinant, a ligand for E- and P-selectin
EW Easton, WE Schiphorst, E van Drunen, CE van der Schoot and DH van den Eijnden
Department of Medical Chemistry, Vrije Universiteit, Amsterdam, The
Netherlands.
The sialyl-Lex determinant (NeuAc alpha 2-->3Gal beta 1-->4[Fuc
alpha- 1-->3]GlcNAc) has been identified as a major ligand in the
selectin- mediated adhesion of neutrophils and monocytes to activated
endothelium or platelets. This carbohydrate epitope is formed by the
sequential action of alpha 3-sialyltransferase and alpha
3-fucosyltransferase on N- acetyllactosamine (Gal beta 1-->4GlcNAc)
disaccharide termini of glycoconjugates. We have addressed the role of the
human myeloid alpha 3-fucosyltransferase in the expression of this epitope
at the leucocyte surface by determining its activity in human-mouse
leukemic cell hybrids (WEGLI), normal human granulocytes and chronic
myeloid leukemia (CML) cells using sialylated and desialylated
glycoproteins and oligosaccharides as acceptor substrates. In contrast to
what has been reported for the myeloid-type enzyme, we found that the alpha
3- fucosyltransferase of the cells studied can use sialylated acceptors be
it that the activity is several times lower than with asialo- substrates.
Characterization of the product obtained with a sialylated oligosaccharide
indicated that the enzyme can catalyze the formation of the sialyl-Le(x)
structure. Flow cytometry of the WEGLI cells using a sialyl-Le(x)-specific
monoclonal antibody (MoAb) showed that these cells indeed express
sialyl-Lex at their surface, provided that they contain human chromosome
11. Earlier the presence of this chromosome had been correlated with the
expression of alpha 3-fucosyltransferase activity. In addition to
sialyl-Le(x), WEGLI cells containing chromosome 11 showed high-expression
levels of related structures recognized by antibodies VIM-2 and VIM-8,
suggesting that fucose addition can occur at both distal and proximal
GlcNAc residues in poly- N-acetyl-lactosaminoglycan sequences. Based on the
human chromosome contents it could be ruled out that the alpha
3-fucosyltransferase of WEGLI cells is a Lewis-type alpha 3/4- or
plasma-type alpha 3- fucosyltransferase, the genes of which have been
mapped to chromosome 19. It is concluded that the enzyme studied is of the
myeloid-type and indeed is involved in the synthesis of sialyl-Le(x) (and
also VIM-2 and VIM-8 structures) in leukocytes provided that its expression
is at a sufficiently high level.
Volume 81,
Issue 11,
pp. 2978-2986,
06/01/1993
Copyright © 1993 by The American Society of Hematology
