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© The Rockefeller University Press, 0021-9525/2001//905 $5.00
The Journal of Cell Biology, Volume 153, Number 5, , 2001 905-916

Inhibition of β₂Integrin–Mediated Leukocyte Cell Adhesion by Leucine–Leucine–Glycine Motif–Containing Peptides

^a Department of Biosciences, Division of Biochemistry
^b VTT Biotechnology, University of Helsinki, FIN-00014 Helsinki, Finland
Department of Biosciences, Division of Biochemistry, University of Helsinki, Viikinkaari 5, FIN-00014 Helsinki, Finland.(358) 9-191-59068(358) 9-191-59023

erkki.koivunen{at}helsinki.fi

Many integrins mediate cell attachment to the extracellular matrix by recognizing short tripeptide sequences such as arginine–glycine–aspartic acid and leucine–aspartate–valine. Using phage display, we have now found that the leukocyte-specific β₂ integrins bind sequences containing a leucine–leucine–glycine (LLG) tripeptide motif. An LLG motif is present on intercellular adhesion molecule (ICAM)-1, the major β₂ integrin ligand, but also on several matrix proteins, including von Willebrand factor. We developed a novel β₂ integrin antagonist peptide CPCFLLGCC (called LLG-C4), the structure of which was determined by nuclear magnetic resonance. The LLG-C4 peptide inhibited leukocyte adhesion to ICAM-1, and, interestingly, also to von Willebrand factor. When immobilized on plastic, the LLG-C4 sequence supported the β₂ integrin–mediated leukocyte adhesion, but not β₁ or β₃ integrin–mediated cell adhesion. These results suggest that LLG sequences exposed on ICAM-1 and on von Willebrand factor at sites of vascular injury play a role in the binding of leukocytes, and LLG-C4 and peptidomimetics derived from it could provide a therapeutic approach to inflammatory reactions.

Key Words: cell adhesion • extracellular matrix • leukocyte • phage display • peptides

© 2001 The Rockefeller University Press

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