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Molecular Pain

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Open Access 01-12-2015 | Research

The opioid peptide dynorphin A induces leukocyte responses via integrin Mac-1 (α_Mβ₂, CD11b/CD18)

Authors: Nataly P. Podolnikova, Julie A. Brothwell, Tatiana P. Ugarova

Published in: Molecular Pain | Issue 1/2015

Abstract

Background

Opioid peptides, including dynorphin A, besides their analgesic action in the nervous system, exert a broad spectrum of effects on cells of the immune system, including leukocyte migration, degranulation and cytokine production. The mechanisms whereby opioid peptides induce leukocyte responses are poorly understood. The integrin Mac-1 (α_Mβ₂, CD11b/CD18) is a multiligand receptor which mediates numerous reactions of neutrophils and monocyte/macrophages during the immune-inflammatory response. Our recent elucidation of the ligand recognition specificity of Mac-1 suggested that dynorphin A and dynorphin B contain Mac-1 recognition motifs and can potentially interact with this receptor.

Results

In this study, we have synthesized the peptide library spanning the sequence of dynorphin AB, containing dynorphin A and B, and showed that the peptides bound recombinant α_MI-domain, the ligand binding region of Mac-1. In addition, immobilized dynorphins A and B supported adhesion of the Mac-1-expressing cells. In binding to dynorphins A and B, Mac-1 cooperated with cell surface proteoglycans since both anti-Mac-1 function-blocking reagents and heparin were required to block adhesion. Further focusing on dynorphin A, we showed that its interaction with the α_MI-domain was activation independent as both the α7 helix-truncated (active conformation) and helix-extended (nonactive conformation) α_MI-domains efficiently bound dynorphin A. Dynorphin A induced a potent migratory response of Mac-1-expressing, but not Mac-1-deficient leukocytes, and enhanced Mac-1-mediated phagocytosis of latex beads by murine IC-21 macrophages.

Conclusions

Together, the results identify dynorphins A and B as novel ligands for Mac-1 and suggest a role for the Dynorphin A-Mac-1 interactions in the induction of nonopiod receptor-dependent effects in leukocytes.

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Title: The opioid peptide dynorphin A induces leukocyte responses via integrin Mac-1 (αMβ2, CD11b/CD18)
Authors: Nataly P. Podolnikova
Julie A. Brothwell
Tatiana P. Ugarova
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Molecular Pain / Issue 1/2015
Electronic ISSN: 1744-8069
DOI: https://doi.org/10.1186/s12990-015-0027-0

2024 ASCO Annual Meeting

Springer Medicine

The opioid peptide dynorphin A induces leukocyte responses via integrin Mac-1 (α_Mβ₂, CD11b/CD18)

Abstract

Background

Results

Conclusions

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Background

Results

Conclusions

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