Opiates impair neutrophil-mediated host defense, but the involvement of κ-opioid receptors in this action has not been defined. The selective κ-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 (pIC50 = 10.40 ± 0.61) and inhibited by naloxone (Ke = 0.27 nM). The κ-opioid receptor agonists bremazocine and ICI-204, 488 also inhibited chemotaxis, as did the respective μ- and δ-opioid receptor agonists [D-Ala2, N-methyl-Phe4, Gly5-ol]enkephalin and [D-Pen2,5]enkephalin albeit with lower potencies. U-50,488H also decreased neutrophil expression of the β2 integrin CD11b/CD18 (Mac-1) and adhesion to plastic in a naloxone-reversible manner. The results indicate that κ-opioid receptors expressed by neutrophils rapidly modulate chemotaxis and adhesion in vitro.
Bibliographical noteFunding Information:
This investigation was supported by NIH grant DA-10200. A. K.-N. is a postdoctoral fellow supported by NIH Psychoneuroimmunology Training grant T32-07239. The authors thank Mrs. Sheila Alexander for her excellent help and advice in FACS analyses.
Copyright 2007 Elsevier B.V., All rights reserved.
- Innate immunity
- Macrophage inflammatory protein