title: Human neutrophil and plasma endopeptidase 24.11: quantification and respective roles in atrial natriuretic peptide hydrolysis.
abstract: Neutral endopeptidase 24.11 activities were quantified on human peripheral blood cell preparations (reflecting the enzyme concentration on the surface of neutrophils) and in the corresponding diluted plasmas by a spectrofluorimetric assay. Despite statistically identical values in both compartments, enzymatic activity towards atrial natriuretic peptide was not comparable. Indeed, incubation of the radiolabelled peptide in whole blood resulted in the thiorphan-sensitive production of the labelled metabolites Phe-Arg-Tyr and the Cys-Phe bond-cleaved peptide. A similar degradation pattern was observed for blood cells but not for plasma, providing evidence for the exclusive involvement of neutrophil endopeptidase in this peptide inactivation. In search for plasma component(s) susceptible to inhibit enzymatic activity, we observed that in the presence of alpha 2-macroglobulin at the physiological concentration of 3.5 mg mL-1, endopeptidase activity decreased from 100% to 51.2 +/- 8.9% (P = 0.002). Our data suggest that this protein could play a role in the endogenous inhibition of plasma endopeptidase activity.
authors.affiliation: Laboratoire Pluridisciplinaire de Recherche Expérimentale Biomédicale, Faculty of Medicine, Université Libre de Bruxelles, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Nortier
authors.forename: S
authors.initials: S
authors.lastname: Pauwels
authors.forename: E
authors.initials: E
authors.lastname: De Prez
authors.forename: M
authors.initials: M
authors.lastname: Deschodt-Lanckman
mesh_terms: D000595:Amino Acid Sequence; D009320:Atrial Natriuretic Factor / Q000097:blood*; D006801:Humans; D006868:Hydrolysis; D008969:Molecular Sequence Data; D015260:Neprilysin / Q000097:blood*; D009504:Neutrophils / Q000201:enzymology*; D009842:Oligopeptides; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification; D012016:Reference Values; D013379:Substrate Specificity; D015244:Thiorphan / Q000494:pharmacology
chemical_list: D009842:Oligopeptides; D010446:Peptide Fragments; D009320:Atrial Natriuretic Factor; D015244:Thiorphan; D015260:Neprilysin