Opioids trigger alpha 5 beta 1 integrin-mediated monocyte adhesion.
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.
Pello
Oscar M
OM
Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Duthey
Béatrice
B
García-Bernal
David
D
Rodríguez-Frade
José Miguel
JM
Stein
Jens V
JV
Teixido
Joaquín
J
Martínez
Carlos
C
Mellado
Mario
M
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology*; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology*; D009294:Narcotics / Q000494:pharmacology*; D051567:Proto-Oncogene Proteins c-vav / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D019061:src-Family Kinases / Q000502:physiology
D039081:Integrin alpha5beta1; D009294:Narcotics; D051567:Proto-Oncogene Proteins c-vav; C107953:RAC1 protein, human; D020881:Enkephalin, D-Penicillamine (2,5)-; D019061:src-Family Kinases; D020830:rac1 GTP-Binding Protein