Human neutrophils as a source of nociceptin: a novel link between pain and inflammation.
Nociceptin is a neuropeptide sharing sequence homology with classical opioid peptides but with a distinct pharmacological profile. Through activation of its receptor, NociR, nociceptin has been linked with several physiological functions in the central nervous system including memory, locomotion, and processing of pain signals. Recently, peripheral blood neutrophils (PMNs) were demonstrated to express a functional NociR, a result suggesting that additional functions of the neuropeptide remain to be elucidated. The present study investigated the possibility that PMNs may be a source of nociceptin and whether the neuropeptide elicits PMN early responses. We observed the presence of nociceptin in the synovial fluids from arthritic patients, an inflammatory milieu typically containing high numbers of PMNs. In addition, freshly isolated PMNs were found to express and secrete nociceptin following degranulation, identifying these inflammatory cells as a novel source of the neuropeptide. Incubation of PMNs with nociceptin elicited a specific pattern of cellular protein phosphorylation on tyrosine residues in a rapid and transient fashion. Moreover, nociceptin prevented intracellular accumulation of cAMP in fMLP-stimulated PMNs, an effect mimicked by the specific NociR synthetic agonist, Ro 64-6198. Taken together, these results show that nociceptin/NociR is present and functional in human neutrophils, and the results identify a novel dialogue pathway between neural and immune tissues.
Fiset
Marie-Elaine
ME
Centre de Recherche en Rhumatologie et Immunologie, Faculté de Médecine, Université Laval, 2705 Laurier Boulevard, Office T1-49, Québec, Canada G1V 4G2.
Gilbert
Caroline
C
Poubelle
Patrice E
PE
Pouliot
Marc
M
D001168:Arthritis / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000378:metabolism*; D018847:Opioid Peptides / Q000378:metabolism*; D010146:Pain / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051572:Proto-Oncogene Proteins c-hck; D011957:Receptors, Opioid / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D013582:Synovial Fluid / Q000737:chemistry / Q000276:immunology; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D000242:Cyclic AMP; D018847:Opioid Peptides; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051572:Proto-Oncogene Proteins c-hck; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C496631:HCK protein, human; C000722283:OPRL1 protein, human