title: Increased expression of an endopeptidase (gamma-EGE/IDE) hydrolyzing beta-endorphin during differentiation and maturation of bone marrow macrophages.
abstract: The presence and regulated expression of peptidase activity is a powerful mechanism with the potential to terminate or alter receptor recognition, cell membrane signal transduction, and physiological responses of immune cells to exogenous opioid peptides. In this study, the expression of an endopeptidase that hydrolyzes beta-endorphin to gamma-endorphin and other peptide products was investigated during in vitro differentiation and maturation of recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) -derived, bone marrow-derived macrophages. In freshly isolated intact isolated mouse bone marrow cells the rate of beta-endorphin hydrolysis is undetectable (<0.1 nmol beta-endorphin hydrolyzed/h/10[6] cells). However, total intracellular beta-endorphin hydrolytic activity was increased significantly to 20.0 +/- 1.7 nmol/h/10(6) cells in the mature mouse macrophages derived in vitro by culture with rGM-CSF. rGM-CSF-derived macrophages expressed significantly higher levels of both protein and mRNA for the major beta-endorphin endopeptidase, gamma-endorphin-generating enzyme/insulin-degrading enzyme (gamma-EGE/IDE). Moreover, this enzymatic activity appears to be responsible for cleavage of exogenous beta-endorphin by intact rGM-CSF-derived macrophages or peritoneal macrophages to generate gamma-endorphin and other peptide products.
authors.affiliation: Department of Biochemistry, The University of Texas Southwestern Medical Center at Dallas, 75235-9038, USA.
authors.forename: B
authors.initials: B
authors.lastname: Sarada
authors.forename: D
authors.initials: D
authors.lastname: Thiele
authors.forename: T
authors.initials: T
authors.lastname: Dang
authors.forename: A
authors.initials: A
authors.lastname: Safavi
authors.forename: L B
authors.initials: LB
authors.lastname: Hersh
authors.forename: G L
authors.initials: GL
authors.lastname: Cottam
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D010450:Endopeptidases / Q000096:biosynthesis*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D008264:Macrophages / Q000166:cytology* / Q000201:enzymology*; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology; D001615:beta-Endorphin / Q000378:metabolism*
chemical_list: D011994:Recombinant Proteins; D001615:beta-Endorphin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010450:Endopeptidases; C043537:gamma-endorphin generating enzyme