The selectin GMP-140 binds to sialylated, fucosylated lactosaminoglycans on both myeloid and nonmyeloid cells.
Granule membrane protein-140 (GMP-140) is an inducible receptor for myeloid leukocytes on activated platelets and endothelium. Like other selectins, GMP-140 recognizes specific oligosaccharide ligands. However, prior data on the nature of these ligands are contradictory. We investigated the structural features required for ligand interaction with GMP-140 using purified GMP-140, cells naturally expressing specific oligosaccharides, and cells expressing cloned glycosyltransferases. Like the related selectin endothelial leukocyte adhesion molecule-1 (ELAM-1), GMP-140 recognizes alpha(2-3)sialylated, alpha(1-3)fucosylated lactosaminoglycans on both myeloid and nonmyeloid cells, including the sequence Neu5Ac alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNac beta-R (sialyl Lewis x). Recognition requires sialic acid, because cells expressing large amounts of Lewis x, but not sialyl Lewis x, do not interact with GMP-140. Although sialyl Lewis x is expressed by both myeloid HL-60 cells and CHO cells transfected with an alpha 1-3/4 fucosyltransferase, GMP-140 binds with significantly higher affinity to HL-60 cells. Thus, the sialyl Lewis x tetrasaccharide may require additional structural modifications or specific presentations in order for leukocytes in flowing blood to interact rapidly and with high affinity to GMP-140 on activated platelets or endothelium.
Zhou
Q
Q
Department of Biochemistry, University of Georgia, Athens 30602.
Moore
K L
KL
Smith
D F
DF
Varki
A
A
McEver
R P
RP
Cummings
R D
RD
D000606:Amino Sugars / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D016466:CHO Cells; D002240:Carbohydrate Sequence; D002460:Cell Line; D006224:Cricetinae; D005643:Fucose / Q000378:metabolism; D006801:Humans; D016256:Lewis X Antigen / Q000378:metabolism; D008969:Molecular Sequence Data; D009439:Neuraminidase / Q000235:genetics / Q000378:metabolism; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism*; D012794:Sialic Acids / Q000378:metabolism*; D014162:Transfection / Q000235:genetics; D014407:Tumor Cells, Cultured
D000606:Amino Sugars; D000911:Antibodies, Monoclonal; D016256:Lewis X Antigen; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D011134:Polysaccharides; D012794:Sialic Acids; C039448:lactosaminoglycan; D005643:Fucose; D009439:Neuraminidase