Opioids Trigger 5beta1 Integrin-Mediated Monocyte Adhesion

Pello OM, Duthey B, Garcia-Bernal D, Rodriguez-Frade JM, Stein JV, Teixido J, Martinez-A C and Mellado M
Source: J Immunol
Publication Date: (2006)
Issue: 176(3): 1675-1685
Research Area:
Immunotherapy / Hematology
Cells used in publication:
MonoMac1 [MM1]
Species: human
Tissue Origin: blood
Nucleofector® I/II/2b
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-alpha(5)beta(1) 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 G(i). These data show that opioids have important implications in regulating leukocyte trafficking, adding a new function to their known effects as immune response modulators.