PEPTIDES WHICH BIND TO E-SELECTIN AND BLOCK NEUTROPHIL ADHESION

E-selectin is an inducible cell adhesion molecule which mediates rolli ng of neutrophils on the endothelium, an early event in the developmen t of an inflammatory response, inhibition of selectin-mediated rolling is a possible means for controlling inflammation-induced diseases, an d several classes of compounds have been tested for this use. We descr ibe here the use of recombinant peptide library screening for identifi cation and optimization of novel ligands which bind to E-selectin. Sev eral of these peptides bind with K-d values in the low nanomolar range and block E-selectin-mediated adhesion of neutrophils in static and f low cell assays. Administration of the peptide to mice undergoing an a cute inflammatory response reduced the extent of neutrophil transmigra tion to the site of inflammation, demonstrating the utility of this co mpound as a potential therapeutic. The identification of a peptide lig and for E-selectin suggests that the complete natural ligand for this adhesion molecule may include protein as well as carbohydrate moieties .