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.
Serhan
C N
CN
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
Fierro
I M
IM
Chiang
N
N
Pouliot
M
M
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