The neutrophil selectin LECAM-1 presents carbohydrate ligands to the vascular selectins ELAM-1 and GMP-140.
LECAM-1 (leukocyte-endothelial cell adhesion molecule 1), the lymphocyte lectin ("selectin") homing receptor for peripheral lymph nodes (PLNs), participates in the earliest interactions of polymorphonuclear neutrophilic leukocytes (PMNs) with inflamed venules. Here, we present evidence that LECAM-1 mediates this function through a novel mechanism--presentation of oligosaccharide ligands to the inducible vascular selectins endothelial-leukocyte adhesion molecule (ELAM-1) and granule membrane protein 140 (GMP-140). PMN, but not lymphocyte, LECAM-1 is modified with the vascular selectin ligand sialyl Lewis x (sLex) and specifically binds ELAM-1-transfected cells. Although only a small fraction of total cell surface sLex, LECAM-1-associated sLex appears to play a prominent role in PMN interactions with cell-associated ELAM-1 and GMP-140, as anti-LECAM-1 monoclonal antibodies or selective removal of cell surface LECAM-1 inhibits PMN binding to vascular selectin transfectants by up to 70%. The enhanced function of LECAM-1-associated sLex may reflect the striking concentration, shown here, of LECAM-1 on PMN surface microvilli, the site of initial cellular contact.
Picker
L J
LJ
Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235-9072.
Warnock
R A
RA
Burns
A R
AR
Doerschuk
C M
CM
Berg
E L
EL
Butcher
E C
EC
D000911:Antibodies, Monoclonal / Q000276:immunology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism; D008970:Molecular Weight; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism; D009844:Oligosaccharides / Q000378:metabolism; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011485:Protein Binding; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism*; D014162:Transfection
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D008024:Ligands; D009844:Oligosaccharides; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D016201:Receptors, Lymphocyte Homing