Effects of endogenous and synthetic opioid peptides on neutrophil function in vitro.
BACKGROUND
Opioid peptides released from immunocytes during inflammation and stress in critically ill patients are associated with an altered immune response. Moreover, concentrations of opioid peptides are increased in peripheral blood and at the sites of inflammatory reactions.


METHODS
Using flow cytometric assay of whole human blood, we investigated direct effects of endogenous and synthetic opioid peptides on surface expression of complement receptors CD35 and CD11b/CD18 and Fcã receptor III CD16, and superoxide anion generation of neutrophils.


RESULTS
The endogenous opioid peptides beta-endorphin(1-31) and met-enkephalin, representing the N-terminal fragment of beta-endorphin(1-31), and the synthetic delta opioid receptor agonists D-Ala(2)-D-Leu(5)-enkephalin and D-Pen(2)-enkephalin produced concentration-dependent stimulation of neutrophil activity. Incubation with met-enkephalin 10(-7) M or beta-endorphin(1-31) 10(-7) M led to an increase in receptor expression of up to 10% (met-enkephalin) and 15% (beta-endorphin(1-31)). After incubation with D-Ala(2)-D-Leu(5)-enkephalin or D-Pen(2/5)-enkephalin, receptor expression was increased by up to 30%. This correlated with concentration-dependent stimulation of the production of reactive oxygen intermediates, as shown by an increase of up to 40% in oxidative burst activity. All effects were abolished after preincubation with naloxone or with the selective delta opioid antagonist naltrindole, whereas the selective micro receptor antagonist d-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2) showed only partial inhibitory effects.


CONCLUSIONS
Our data suggest a delta opioid receptor-mediated stimulatory effect on neutrophil function. beta-Endorphin(27-31), the C-terminal fragment of beta-endorphin(1-31), did not alter neutrophil function, indicating that beta-endorphin(1-31) mediates its effect on neutrophils via the N-terminal fragment. This study may contribute to a better understanding of neuroimmune interaction.
D015703:Antigens, CD / Q000032:analysis; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000276:immunology; D016308:Enkephalin, Leucine-2-Alanine / Q000276:immunology; D004744:Enkephalin, Methionine / Q000276:immunology; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D008297:Male; D018375:Neutrophil Activation; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D018847:Opioid Peptides / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000276:immunology; D013481:Superoxides / Q000378:metabolism; D001615:beta-Endorphin / Q000276:immunology
D015703:Antigens, CD; D018847:Opioid Peptides; D010446:Peptide Fragments; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D013481:Superoxides; D013004:Somatostatin; D004744:Enkephalin, Methionine; D001615:beta-Endorphin; D016308:Enkephalin, Leucine-2-Alanine; D020881:Enkephalin, D-Penicillamine (2,5)-