Increased expression of an endopeptidase (γ-EGE/IDE) hydrolyzing β- endorphin during differentiation and maturation of bone marrow macrophages

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 β-endorphin to γ-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 β-endorphin hydrolysis is undetectable (<0.1 nmol β-endorphin hydrolyzed/h/10⁶ cells). However, total intracellular β-endorphin hydrolytic activity was increased significantly to 20.0 ± 1.7 nmol/h/10⁶ 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 β-endorphin endopeptidase, γ-endorphin-generating enzyme/insulin-degrading enzyme (γ-EGE/IDE). Moreover, this enzymatic activity appears to be responsible for cleavage of exogenous β-endorphin by intact rGM-CSF-derived macrophages or peritoneal macrophages to generate γ- endorphin and other peptide products.