Neutrophil neutral endopeptidase variation and its regulation by opioid peptides

The opioid peptide methionine-enkephalin (MENK) has significant immunomodul atory ability in addition to its neurotransmitter function. Since neutral e ndopeptidase (NEP, CD10, enkephalinase EC 3.4.24.11) cleaves opioid peptide s, the presence and activity of NEP in neutrophils from different persons m ight be responsible for the diverse, neuropeptide-induced, responses of neu trophils from different donors [Ann. N. Y. Acad. Sci. 650 (1992) 146]. The results obtained showed statistically significant differences in NEP activi ty among donors (high, medium and low). A 10-fold higher NEP activity in ne utrophils (160-280 nmol/10(6) cells/h) and in their corresponding membrane preparations (550 nmol/mg protein/min) in our study, as compared to literat ure data, was a result of high specificity and affinity of Suc-Ala-Ala-Phe- pNA as substrate. In control nontreated neutrophils. the number of CD10 pos itive cells were not correlated with NEP activity. However, in neutrophils treated with a physiological (10(-10) M) concentration of MENK, two main ev ents occurred: not only did the number of CD10 positive cells correlate wit h NEP activity, but contrary to control samples, MENK upregulated the expre ssion of CD10 marker as demonstrated by an increase of mean florescence int ensity (F-mean) in donors with low NEP activity. Taken together, these data add some clarity to the diverse activity of enkephalins in association wit h enzyme cleavage of those molecules. (C) 2001 Elsevier Science B.V. All ri ghts reserved.