TY - JOUR
T1 - The neutrophil selectin LECAM-1 presents carbohydrate ligands to the vascular selectins ELAM-1 and GMP-140
AU - Picker, Louis J.
AU - Warnock, R. Aaron
AU - Burns, Alan R.
AU - Doerschuk, Claire M.
AU - Berg, Ellen L.
AU - Butchert, Eugene C.
N1 - Funding Information:
The authors gratefully acknowledge the superb technical assistance of B. Ferguson-Darnell, P. Collins, J. Treer, and S. Greene; the generosity of Drs. C. W. Smith, 8. Seed, J. Harlan, and P. Terasaki for their provision of reagents; and the vital contribution of M. Robinson in the production of the stable ElAM-1 transfectants. We also thank Drs. T. K. Kishimoto, C. W. Smith, M. Jutila, and N. Oppenheimer-Marks for their helpful discussions during the execution of this project. This study was supported by funds from the Department of Pathology, Uni-versityof TexasSouthwestern Medical Center; by NIH grants A119957, GM41965 and GM37734; and by University of California at Berkeley Tobacco-Related Research Award #RT454. C. M. D. is aCareer Investigator of the American Lung Association. A. R. B. is the recipient of a student fellowship from the Medical Research Council of Canada. E. L. 8. is a Senior Fellow of the Leukemia Society. E. C. B. is an Established Investigator of the American Heart Association.
PY - 1991/9/6
Y1 - 1991/9/6
N2 - 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 venuies. 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.
AB - 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 venuies. 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.
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U2 - 10.1016/0092-8674(91)90438-5
DO - 10.1016/0092-8674(91)90438-5
M3 - Article
C2 - 1716182
AN - SCOPUS:0025939215
SN - 0092-8674
VL - 66
SP - 921
EP - 933
JO - Cell
JF - Cell
IS - 5
ER -