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

Erkki Koivunen (Corresponding Author), Tanja-Maria Ranta, Arto Annila, Seija Taube, Asko Uppala, Marjukka Jokinen, Gijsbert van Willigen, Eveliina Ihanus, Carl Gahmberg

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Abstract

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.
Original languageEnglish
Pages (from-to)905-915
JournalJournal of Cell Biology
Volume153
Issue number5
DOIs
Publication statusPublished - 2001
MoE publication typeA1 Journal article-refereed

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    Koivunen, E., Ranta, T-M., Annila, A., Taube, S., Uppala, A., Jokinen, M., van Willigen, G., Ihanus, E., & Gahmberg, C. (2001). Inhibition of β2Integrin–Mediated Leukocyte Cell Adhesion by Leucine–Leucine–Glycine Motif–Containing Peptides. Journal of Cell Biology, 153(5), 905-915. https://doi.org/10.1083/jcb.153.5.905