β-Glucosidase inhibition in murine peritoneal macrophages by conduritol-B-epoxide: an in vitro model of the Gaucher cell

Abstract

Murine peritoneal macrophages were cultured in the presence of conduritol-B-epoxide, a specific covalent inhibitor of β-glucosidase. The inhibition was found to be dose and time dependent. Upon removal of the inhibitor from the culture medium, β-glucosidase activity recovered to half maximum by 2.2 days. Treatment of macrophages with this inhibitor for 15 days did not affect cell viability, lysosomal enzyme release to the medium, or levels of intracellular lysosomal enzymes, other than β-glucosidase activity. This inhibition results in the accumulation of glucocerebroside. In vitro studies on the pathobiology of such macrophages whose β-glucosidase activity has been reduced may be useful toward understanding the pathogenesis of Gaucher disease. © 1986.