title: Gaucher-like changes in human blood-derived macrophages induced by beta-glucocerebrosidase inhibition.
abstract: Human blood-derived macrophages were cultured in the presence of conduritol-B-epoxide, a specific inhibitor of beta-glucosidase, to induce changes resembling those occurring in the cells of patients with Gaucher's disease. After 24 hours of incubation, only 5% of the original beta-glucosidase activity remained; on removal of the inhibitor, the enzyme activity recovered almost fully to control levels after 5 days. After 30 days of incubation with conduritol-B-epoxide, the macrophages contained almost 10 times as much glucocerebroside as the untreated controls, and the cells displayed morphologic changes reminiscent of Gaucher's cells. This in vitro system may enable detailed studies on the pathogenetic mechanisms associated with glucocerebroside accumulation in human macrophages as well as on the turnover of the accumulated substrate and reversal of the morphologic abnormalities on removal of the inhibitor.
authors.affiliation: Department of Pediatrics, Hadassah University Hospital Medical School, Jerusalem.
authors.forename: S
authors.initials: S
authors.lastname: Yatziv
authors.forename: D S
authors.initials: DS
authors.lastname: Newburg
authors.forename: N
authors.initials: N
authors.lastname: Livni
authors.forename: G
authors.initials: G
authors.lastname: Barfi
authors.forename: E H
authors.initials: EH
authors.lastname: Kolodny
mesh_terms: D001773:Blood Cells / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D005776:Gaucher Disease / Q000473:pathology*; D005959:Glucosidases / Q000037:antagonists & inhibitors*; D005962:Glucosylceramidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007294:Inositol / Q000031:analogs & derivatives / Q000494:pharmacology; D008264:Macrophages / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D008854:Microscopy, Electron
chemical_list: D007294:Inositol; D005959:Glucosidases; D005962:Glucosylceramidase; C011423:conduritol epoxide