Opioid receptors on bone marrow neutrophils modulate chemotaxis and CD11b/CD18 expression.
Opiates impair neutrophil-mediated host defense, but the involvement of kappa-opioid receptors in this action has not been defined. The selective kappa-opioid receptor agonist [trans-(+)3,4-dichloro-N-methyl-N[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide methanesulfonate inhibited macrophage inflammatory protein-2-induced chemotaxis of bone marrow neutrophils from C57BL/6 mice. Its effects were concentration-dependent (pIC(50)=10.40+/-0.61) and inhibited by naloxone (K(e)=0.27 nM). The kappa-opioid receptor agonists bremazocine and ICI-204, 488 also inhibited chemotaxis, as did the respective mu- and delta-opioid receptor agonists [D-Ala(2), N-methyl-Phe(4), Gly(5)-ol]enkephalin and [D-Pen(2,5)]enkephalin albeit with lower potencies. U-50,488H also decreased neutrophil expression of the beta(2) integrin CD11b/CD18 (Mac-1) and adhesion to plastic in a naloxone-reversible manner. The results indicate that kappa-opioid receptors expressed by neutrophils rapidly modulate chemotaxis and adhesion in vitro.
Department of Veterinary PathoBiology, University of Minnesota, 1988 Fitch Avenue, St. Paul, MN 55108-6010, USA.
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Kulkarni-Narla
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Walcheck
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Brown
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism; D018821:CD18 Antigens / Q000187:drug effects* / Q000378:metabolism; D054426:Chemokine CXCL2; D018925:Chemokines; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D016177:Macrophage-1 Antigen / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000187:drug effects* / Q000378:metabolism
D018712:Analgesics, Non-Narcotic; D018821:CD18 Antigens; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D016177:Macrophage-1 Antigen; D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; D009270:Naloxone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer