Macrophages exposed in vitro to conduritol B epoxide resemble Gaucher cells.
In Gaucher disease the genetic lack of acid beta-glucosidase activity causes glucocerebroside to accumulate in the lysosomes of macrophage-derived cells, producing large characteristic Gaucher cells. The formation of Gaucher cells seems to be central to the pathobiology of this lysosomal storage disease. To develop a model simulating this process, cultured murine peritoneal macrophages were treated with conduritol B epoxide, a specific irreversible inhibitor of acid beta-glucosidase, for 6, 15, and 24 days. The conduritol B epoxide-treated macrophages accumulated glucocerebroside as a function of time, progressing to a fivefold elevation over control values after 24 days of treatment. Electron microscopy of the cells treated for 24 days reveals characteristics of Gaucher cells, including striations consisting of oriented fibrils. With conventional staining techniques, these fibrils have an appearance considered highly characteristic of Gaucher disease. Thus, macrophages treated with conduritol B epoxide are a useful model for studying the metabolic consequences and morphologic features associated with glucocerebroside accumulation in Gaucher cells.
Newburg
D S
DS
Department of Biochemistry, E.K. Shriver Center for Mental Retardation, Waltham, Massachusetts 02254.
Shea
T B
TB
Yatziv
S
S
Raghavan
S S
SS
McCluer
R H
RH
D000818:Animals; D005776:Gaucher Disease / Q000473:pathology; D005959:Glucosidases / Q000037:antagonists & inhibitors*; D005962:Glucosylceramidase / Q000037:antagonists & inhibitors*; D005963:Glucosylceramides / Q000378:metabolism; D007294:Inositol / Q000031:analogs & derivatives* / Q000494:pharmacology; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL
D005963:Glucosylceramides; D007294:Inositol; D005959:Glucosidases; D005962:Glucosylceramidase; C011423:conduritol epoxide