B. Sarada et al., INCREASED EXPRESSION OF AN ENDOPEPTIDASE (GAMMA-EGE IDE) HYDROLYZING BETA-ENDORPHIN DURING DIFFERENTIATION AND MATURATION OF BONE-MARROW MACROPHAGES/, Journal of leukocyte biology, 62(6), 1997, pp. 753-760
The presence and regulated expression of peptidase activity is a power
ful mechanism with the potential to terminate or alter receptor recogn
ition, cell membrane signal transduction, and physiological responses
of immune cells to exogenous opioid peptides, In this study, the expre
ssion of an endopeptidase that hydrolyzes beta-endorphin to gamma-endo
rphin and other peptide products was investigated during in vitro diff
erentiation and maturation of recombinant ganulocyte-macrophage colony
-stimulating factor (rGM-CSF) -derived, bone marrow-derived macrophage
s. In freshly isolated intact isolated mouse bone marrow cells the rat
e of beta-endorphin hydrolysis is undetectable (<0.1 nmol beta-endorph
in hydrolyzed/h/10(6) cells), However, total intracellular beta-endorp
hin hydrolytic activity was increased significantly to 20.0 +/- 1.7 nm
ol/h/10(6) cells in the mature mouse macrophages derived in vitro by c
ulture with rGM-CSF. rGM-CSF-derived macrophages expressed significant
ly higher levels of both protein and mRNA for the major beta-endorphin
endopeptidase, gamma-endorphin-generating enzyme/insulin-degrading en
zyme (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-endor
phin and other peptide products.