Species-specific and conserved epitopes on mouse and human E-selectin important for leukocyte adhesion.
Selectins are C-type, cell surface lectins that are key players in leukocyte adhesion to the blood vessel wall endothelium. We describe here epitopes for a series of novel monoclonal antibodies (moAbs), UZ4-UZ7, directed against mouse E-selectin. All four antibodies specifically bind to mouse E-selectin, but not to P- or L-selectin, and all inhibit the adhesion of granulocytes, peripheral blood lymphocytes, and promyelocytic HL-60 cells to cytokine-activated mouse endothelium. Three moAbs, UZ5, UZ7, and UZ6, specifically inhibit mouse E-selectin-mediated adhesion by binding to epitopes in domains CR1 or CR2. moAb UZ4 inhibits leukocyte adhesion to both human and murine endothelium activated with IL-1 or other proinflammatory stimuli. UZ4 is the first described moAb that detects an epitope in the lectin domain which is conserved in both murine and human E-selectin (CXKKKL), but is not present in the other members of the selectin family, P- and L-selectin. Interestingly, UZ5, UZ6, and UZ7 more efficiently interfere with lymphocyte than with granulocyte adhesion to cytokine-activated endothelium, while UZ4 completely blocks adhesion of PMN, lymphocytes, and HL-60 and U937 cell lines. The data suggest that E-selectin-ligand engagement differs between lymphocytes and PMN, and that these differences may be accentuated by the CR1 and CR2 domains in the E-selectin cell adhesion molecule.
Hammel
M
M
Experimental Medicine I, University Erlangen-Nürnberg, Erlangen, Germany.
Weitz-Schmidt
G
G
Krause
A
A
Moll
T
T
Vestweber
D
D
Zerwes
H G
HG
Hallmann
R
R
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015153:Blotting, Western; D002448:Cell Adhesion; D002478:Cells, Cultured; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000378:metabolism; D019040:E-Selectin / Q000737:chemistry* / Q000276:immunology; D004730:Endothelium, Vascular / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry*; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D037102:Lectins / Q000737:chemistry; D007962:Leukocytes / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013997:Time Factors; D014162:Transfection; D014471:Umbilical Veins / Q000166:cytology
D000911:Antibodies, Monoclonal; D018076:DNA, Complementary; D019040:E-Selectin; D000939:Epitopes; D037102:Lectins