Cutting edge: nociceptin stimulates neutrophil chemotaxis and recruitment: inhibition by aspirin-triggered-15-epi-lipoxin A4.
The nociceptin receptor (Noci-R) is a G protein-coupled receptor present in neural tissues and its activation by nociceptin is involved in the processing of pain signals. Here, we report that Noci-R is present and functional on peripheral blood polymorphonuclear leukocytes (PMN). Human PMN express mRNA for Noci-R, its nucleotide sequence determined, and specific binding with [(125)I]-labeled nociceptin gave an apparent K(d) approximately 1.5 nM for this PMN opioid receptor. Nociceptin evoked PMN chemotaxis with maximal activity at 100 pM, without intracellular Ca(2+) mobilization. When injected in murine air pouches, nociceptin elicited leukocyte infiltration in a concentration-dependent fashion. Nociceptin-stimulated PMN infiltration was inhibited by treating mice with a synthetic analog of the aspirin-triggered lipid mediator 15-epi-lipoxin A(4). The present results identify nociceptin as a potent chemoattractant and provide a novel link between the neural and immune systems that are blocked by aspirin-triggered lipid mediators and may be relevant in neurogenic inflammation.
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. cnserhan@zeus.bwh.harvard.edu
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Serhan
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Fierro
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Chiang
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Pouliot
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology*; D020013:Calcium Signaling; D002465:Cell Movement / Q000502:physiology; D002630:Chemotactic Factors / Q000037:antagonists & inhibitors / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000502:physiology*; D007271:Injections, Intradermal; D007424:Intracellular Fluid / Q000502:physiology; D044045:Lipoxins; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018847:Opioid Peptides / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011957:Receptors, Opioid / Q000096:biosynthesis / Q000235:genetics; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001241:Aspirin; D002630:Chemotactic Factors; D006893:Hydroxyeicosatetraenoic Acids; D044045:Lipoxins; D018847:Opioid Peptides; D012333:RNA, Messenger; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C040527:lipoxin A4