Peptides Which Bind to E-selectin and Block Neutrophil Adhesion (∗)

E-selectin is an inducible cell adhesion molecule which mediates rolling of neutrophils on the endothelium, an early event in the development of an inflammatory response. Inhibition of selectin-mediated rolling is a possible means for controlling inflammation-induced diseases, and several classes of...

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Bibliographic Details
Published in:The Journal of biological chemistry 1995-09, Vol.270 (36), p.21129-21136
Main Authors: Martens, Christine L., Cwirla, Steven E., Lee, Rozanne Y.-W., Whitehorn, Erik, Chen, Esther Y.-F., Bakker, Alice, Martin, Edith L., Wagstrom, Christopher, Gopalan, Priya, Smith, C. Wayne, Tate, Emily, Koller, Kerry J., Schatz, Peter J., Dower, William J., Barrett, Ronald W.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Cell Adhesion - drug effects
Cell Adhesion Molecules - metabolism
E-Selectin
Female
Humans
Ligands
Mice
Mice, Inbred BALB C
Molecular Sequence Data
Mutagenesis
Neutrophils - cytology
Neutrophils - drug effects
Peptides - chemical synthesis
Peptides - metabolism
Peptides - pharmacology
Protein Binding
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
Recombinant Proteins - pharmacology
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Summary:E-selectin is an inducible cell adhesion molecule which mediates rolling of neutrophils on the endothelium, an early event in the development of an inflammatory response. Inhibition of selectin-mediated rolling is a possible means for controlling inflammation-induced diseases, and several classes of compounds have been tested for this use. We describe here the use of recombinant peptide library screening for identification and optimization of novel ligands which bind to E-selectin. Several of these peptides bind with Kd values in the low nanomolar range and block E-selectin-mediated adhesion of neutrophils in static and flow-cell assays. Administration of the peptide to mice undergoing an acute inflammatory response reduced the extent of neutrophil transmigration to the site of inflammation, demonstrating the utility of this compound as a potential therapeutic. The identification of a peptide ligand for E-selectin suggests that the complete natural ligand for this adhesion molecule may include protein as well as carbohydrate moieties.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.270.36.21129