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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
Original Article |
Inhibition of β2Integrin–Mediated Leukocyte Cell Adhesion by Leucine–Leucine–Glycine Motif–Containing Peptides
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
Abbreviations used in this paper: GST, glutathione S-transferase; ICAM, intercellular adhesion molecule; LLG, leucine–leucine–glycine; NMR, nuclear magnetic resonance; nOe, nuclear Overhauser enhancement; RGD, arginine–glycine–aspartic acid; TNF, tumor necrosis factor.
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