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Inhibition of β(2)Integrin–Mediated Leukocyte Cell Adhesion by Leucine–Leucine–Glycine Motif–Containing Peptides

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 β(2) integrins bind sequences containing a leucine–leuc...

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Detalles Bibliográficos
Autores principales: Koivunen, Erkki, Ranta, Tanja-Maria, Annila, Arto, Taube, Seija, Uppala, Asko, Jokinen, Marjukka, van Willigen, Gijsbert, Ihanus, Eveliina, Gahmberg, Carl G.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2001
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174336/
https://www.ncbi.nlm.nih.gov/pubmed/11381078
Descripción
Sumario: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 β(2) integrins bind sequences containing a leucine–leucine–glycine (LLG) tripeptide motif. An LLG motif is present on intercellular adhesion molecule (ICAM)-1, the major β(2) integrin ligand, but also on several matrix proteins, including von Willebrand factor. We developed a novel β(2) 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 β(2) integrin–mediated leukocyte adhesion, but not β(1) or β(3) 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.