engleski

Met-enkephalin enhances cytotoxic activity of mouse peritoneal macrophages in vivo

Met-enkephalin modulates several functions of macrophages in vitro by binding to opioid receptors expressed on them. However, there is a paucity of data on its ability to alter macrophage functions in vivo. In this study, we examined the effect of single systemic (i/p) injection of Met-enkephalin (MENK) into CBA mice on the cytotoxic activity and NO^-secretion of peritoneal macrophages. Involvement of opioid receptors in the MENK action was tested by using opioid receptor antagonist, naloxone (Nx). Peritoneal macrophages were collected 5 days after glycogen injection (0.5 ml of the 0.12% solution, i/p), and 12 hours after MENK (2.5 mg/kg) injection. Nx (2.5, 5 or 10 mg/kg, i/p) was administered 20 min before MENK. Cytotoxic activity was determined by using L-929 cells as targets. After a 24 hour incubation with various concentrations of macrophages, the proportion of viable L-929 cells was determined by a colorimetric method, using WST-1. NO^- was determined by the method of Naslund et al. (Inf. Immune., 63: 1298, 1995). MENK significantly enhanced cytotoxic activity of peritoneal macrophages. This was associated with enhanced NO^- production. MENK-induced effects were completely (NO^- release) or partly (cytotoxicity) reversed by naloxone (10 mg/kg). However, naloxone by itself acted as an agonist, enhancing macrophage cytotoxicity. Lower Nx doses (2.5 and 5 mg/kg) had lower agonistic activity, but were inactive with regard to the antagonistic ability. The necessity for a relatively high naloxone concentration for the reversion of the MENK-induced enhancement of macrophage cytotoxicity suggests involvement of d opioid receptors. In conclusion, in vivo administration of MENK stimulates the cytotoxicity and NO^- release by peritoneal macrophages. Both effects could be at least partly reversed by naloxone in high concentration, suggesting involvement of d opioid receptors.

Met-enkephalin; macrophage cytotoxicity; NO; opioid receptors

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