Dynorphin and Related Opioid Peptides Enhance Tumoricidal Activity Mediated by Murine Peritoneal Macrophages
The influence of dynorphin A (DYN) and related opioid peptides on the tumoricidal function of activated murine peritoneal exudate macrophages (PEM) was investigated. Addition of DYN to macrophage cultures previously activated with mixed α + β-inter-feron (IFN-α/β) and bacterial lipopolysaccharide (LPS) significantly enhanced their ability to lyse P815 murine mastocytoma cells in a 16 hr chromium-release assay. The effects of DYN were dependent on prior macrophage activation. Peptide subfragments of DYN were effective in a manner similar to that of the 17-amino-acid parent molecule, indicating that peptide interaction with either κ or δ-opioid receptors on the effector cell is effective in potentiating lytic function. The involvement of opiate receptors was confirmed by inhibition of the effects of DYN and leucine enkephalin by the opioid receptor antagonist naloxone. Finally, in addition to IFN-α/β-primed macrophages, DYN also augmented tumoricidal function in PEM primed for cytotoxicity by either γ-interferon (IFN-γ) or the calcium ionophore A23187, Indicating that DYN potentiates function in activated macrophages independent of the specific mode of activation.