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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...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2001
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174336/ https://www.ncbi.nlm.nih.gov/pubmed/11381078 |
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author | Koivunen, Erkki Ranta, Tanja-Maria Annila, Arto Taube, Seija Uppala, Asko Jokinen, Marjukka van Willigen, Gijsbert Ihanus, Eveliina Gahmberg, Carl G. |
author_facet | Koivunen, Erkki Ranta, Tanja-Maria Annila, Arto Taube, Seija Uppala, Asko Jokinen, Marjukka van Willigen, Gijsbert Ihanus, Eveliina Gahmberg, Carl G. |
author_sort | Koivunen, Erkki |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2174336 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2001 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21743362008-05-01 Inhibition of β(2)Integrin–Mediated Leukocyte Cell Adhesion by Leucine–Leucine–Glycine Motif–Containing Peptides Koivunen, Erkki Ranta, Tanja-Maria Annila, Arto Taube, Seija Uppala, Asko Jokinen, Marjukka van Willigen, Gijsbert Ihanus, Eveliina Gahmberg, Carl G. J Cell Biol Original Article 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. The Rockefeller University Press 2001-05-28 /pmc/articles/PMC2174336/ /pubmed/11381078 Text en © 2001 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Original Article Koivunen, Erkki Ranta, Tanja-Maria Annila, Arto Taube, Seija Uppala, Asko Jokinen, Marjukka van Willigen, Gijsbert Ihanus, Eveliina Gahmberg, Carl G. Inhibition of β(2)Integrin–Mediated Leukocyte Cell Adhesion by Leucine–Leucine–Glycine Motif–Containing Peptides |
title | Inhibition of β(2)Integrin–Mediated Leukocyte Cell Adhesion by Leucine–Leucine–Glycine Motif–Containing Peptides |
title_full | Inhibition of β(2)Integrin–Mediated Leukocyte Cell Adhesion by Leucine–Leucine–Glycine Motif–Containing Peptides |
title_fullStr | Inhibition of β(2)Integrin–Mediated Leukocyte Cell Adhesion by Leucine–Leucine–Glycine Motif–Containing Peptides |
title_full_unstemmed | Inhibition of β(2)Integrin–Mediated Leukocyte Cell Adhesion by Leucine–Leucine–Glycine Motif–Containing Peptides |
title_short | Inhibition of β(2)Integrin–Mediated Leukocyte Cell Adhesion by Leucine–Leucine–Glycine Motif–Containing Peptides |
title_sort | inhibition of β(2)integrin–mediated leukocyte cell adhesion by leucine–leucine–glycine motif–containing peptides |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174336/ https://www.ncbi.nlm.nih.gov/pubmed/11381078 |
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