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
Number of pages11
JournalJournal of Cell Biology
Volume153
Issue number5
DOIs
Publication statusPublished - 2001
MoE publication typeA1 Journal article-refereed

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Cell Adhesion
Integrins
von Willebrand Factor
Leukocytes
Intercellular Adhesion Molecule-1
Peptides
Peptidomimetics
Vascular System Injuries
Bacteriophages
Plastics
Extracellular Matrix
Magnetic Resonance Spectroscopy
Ligands
Acids
Proteins
Therapeutics

Cite this

Koivunen, E., Ranta, T-M., Annila, A., Taube, S., Uppala, A., Jokinen, M., ... 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
Koivunen, Erkki ; Ranta, Tanja-Maria ; Annila, Arto ; Taube, Seija ; Uppala, Asko ; Jokinen, Marjukka ; van Willigen, Gijsbert ; Ihanus, Eveliina ; Gahmberg, Carl. / Inhibition of β2Integrin–Mediated Leukocyte Cell Adhesion by Leucine–Leucine–Glycine Motif–Containing Peptides. In: Journal of Cell Biology. 2001 ; Vol. 153, No. 5. pp. 905-915.
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title = "Inhibition of β2Integrin–Mediated Leukocyte Cell Adhesion by Leucine–Leucine–Glycine Motif–Containing Peptides",
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.",
author = "Erkki Koivunen and Tanja-Maria Ranta and Arto Annila and Seija Taube and Asko Uppala and Marjukka Jokinen and {van Willigen}, Gijsbert and Eveliina Ihanus and Carl Gahmberg",
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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, vol. 153, no. 5, pp. 905-915. https://doi.org/10.1083/jcb.153.5.905

Inhibition of β2Integrin–Mediated Leukocyte Cell Adhesion by Leucine–Leucine–Glycine Motif–Containing Peptides. / Koivunen, Erkki (Corresponding Author); Ranta, Tanja-Maria; Annila, Arto; Taube, Seija; Uppala, Asko; Jokinen, Marjukka; van Willigen, Gijsbert; Ihanus, Eveliina; Gahmberg, Carl.

In: Journal of Cell Biology, Vol. 153, No. 5, 2001, p. 905-915.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Inhibition of β2Integrin–Mediated Leukocyte Cell Adhesion by Leucine–Leucine–Glycine Motif–Containing Peptides

AU - Koivunen, Erkki

AU - Ranta, Tanja-Maria

AU - Annila, Arto

AU - Taube, Seija

AU - Uppala, Asko

AU - Jokinen, Marjukka

AU - van Willigen, Gijsbert

AU - Ihanus, Eveliina

AU - Gahmberg, Carl

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

U2 - 10.1083/jcb.153.5.905

DO - 10.1083/jcb.153.5.905

M3 - Article

VL - 153

SP - 905

EP - 915

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 5

ER -