The role of aminopeptidase N in Met-enkephalin modulated superoxide anion release

We have previously shown that methionine-enkephalin (MENK) alters in dose-d ependent fashion the capacity of human neutrophils to produce superoxide an ion. The response of neutrophils from different donors was diverse and this effect could be due to variable activity of proteolytic enzymes involved i n the degradation of the neuropeptide. In this study, we have demonstrated a highly individual aminopeptidase N (APN) activity of neutrophils from dif ferent donors. Preincubation of neutrophils with MENK, but not with the syn thetic agonist of the mu (DAGO) or the delta (DPDPE) opioid receptor, down- regulated the APN activity. This was paralleled by a loss in cell surface e xpression of APN at physiological (10(-10) M) concentrations of MENK. The l evel of APN activity from different donors correlated with the effect of ME NK on superoxide anion release. Neutrophils with low APN activity, if prein cubated with MENK, released reduced amounts of superoxide anion. In contras t, neutrophils with high APN activity released increased amounts of superox ide anion after preincubation with MENK. Thus, the highly individual APN ac tivity on the surface of neutrophils from different donors seems to be alte red by MENK and to be related to the respiratory burst. (C) 1999 Elsevier S cience B.V. All rights reserved.