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 leukocyt e adhesion to the blood vessel wall endothelium. We describe here epitopes for a series of novel monoclonal antibodies (moAbs), UZ4-UZ7, directed agai nst mouse E-selectin. All four antibodies specifically bind to mouse E-sele ctin, but not to P- or L-selectin, and all inhibit the adhesion of granuloc ytes, peripheral blood lymphocytes, and promyelocytic HL-60 cells to cytoki ne-activated mouse endothelium. Three moAbs, UZ5, UZ7, and UZ6, specificall y inhibit mouse E-selectin-mediated adhesion by binding to epitopes in doma ins CR1 or CR2. moAb UZ4 inhibits leukocyte adhesion to both human and muri ne endothelium activated with IL-I or other proinflammatory stimuli. UZ4 is the first described moAb that detects an epitope in the lectin domain whic h is conserved in both murine and human E-selectin (CXKKKL), but is not pre sent in the other members of the selectin family, P- and L-selectin. Intere stingly, UZ5, UZ6, and UZ7 more efficiently interfere with lymphocyte than with granulocyte adhesion to cytokine-activated endothelium, while UZ4 comp letely blocks adhesion of PAIN, lymphocytes, and HL-60 and U937 cell lines. The data suggest that E-selectin-ligand engagement differs between lymphoc ytes and PMN, and that these differences may be accentuated by the CR1 and CR2 domains in the E-selectin cell adhesion molecule. (C) 2001 Academic Pre ss.