Opioids trigger alpha 5 beta 1 integrin-mediated monocyte adhesion

Pello, Oscar M; Duthey, Béatrice; García-Bernal, David; Rodríguez-Frade, José Miguel; Stein, Jens V; Teixido, Joaquín; Martínez, Carlos; Mellado, Mario (2006). Opioids trigger alpha 5 beta 1 integrin-mediated monocyte adhesion. Journal of immunology, 176(3), pp. 1675-85. Bethesda, Md.: American Association of Immunologists

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Inflammatory reactions involve a network of chemical and molecular signals that initiate and maintain host response. In inflamed tissue, immune system cells generate opioid peptides that contribute to potent analgesia by acting on specific peripheral sensory neurons. In this study, we show that opioids also modulate immune cell function in vitro and in vivo. By binding to its specific receptor, the opioid receptor-specific ligand DPDPE triggers monocyte adhesion. Integrins have a key role in this process, as adhesion is abrogated in cells treated with specific neutralizing anti-alpha5beta1 integrin mAb. We found that DPDPE-triggered monocyte adhesion requires PI3Kgamma activation and involves Src kinases, the guanine nucleotide exchange factor Vav-1, and the small GTPase Rac1. DPDPE also induces adhesion of pertussis toxin-treated cells, indicating involvement of G proteins other than Gi. These data show that opioids have important implications in regulating leukocyte trafficking, adding a new function to their known effects as immune response modulators.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute
UniBE Contributor:	Stein, Jens Volker
ISSN:	0022-1767
ISBN:	16424197
Publisher:	American Association of Immunologists
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:45
Last Modified:	05 Dec 2022 14:14
PubMed ID:	16424197
Web of Science ID:	000234766600046
URI:	https://boris.unibe.ch/id/eprint/18601 (FactScience: 802)