Previous studies have shown that cultured fibroblasts derived from patients with 
genetic defects in lysosomal acid lipase (i. e. the Wolman Syndrome and 
Cholesteryl Ester Storage Disease) are defective in their ability to hydrolyze 
the cholesteryl esters contained in plasma low density lipoprotein (LDL). As a 
result, these mutant cells show a reduced responsiveness to the regulatory 
actions of LDL, as evidenced by a decreased LDL-mediated suppression of the 
activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase and by a decreased 
LDL-mediated activation of cellular cholesteryl ester formation. In the current 
studies, the Wolman Syndrome and Cholesteryl Ester Storage Disease cells were 
grown in the same Petri dish with mutant fibroblasts derived from a patient with 
the homozygous form of Familial Hypercholesterolemia. Whereas pure monolayers of 
either the Familial Hypercholesterolemia cells (lacking cell surface LDL 
receptors) or the acid lipase-deficient cells (lacking cholesteryl ester 
hydrolase activity) responded poorly to LDL, the mixed monolayers developed 
lipoprotein responsiveness as measured by an enhancement of both LDL-mediated 
suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and 
LDL-mediated stimulation of cholesteryl ester formation. This effect was shown 
to result from the release of the lysosomal acid lipase from the Familial 
Hypercholesterolemia homozygote cells into the culture medium and its subsequent 
uptake by the acid lipase-deficient cells. The acquisition of this acid lipase 
activity enhanced the ability of the Wolman Syndrome and Cholesteryl Ester 
Storage Disease cells to respond to the lipoprotein by suppression of 
3-hydroxy-3-methylglutaryl coenzyme A reductase and activation of cellular 
cholesteryl ester formation. These data emphasize the importance of the 
lysosomal acid lipase in the cellular metabolism of LDL cholesteryl esters and, 
in addition, demonstrate that delivery of this enzyme to genetically deficient 
cells can enhance the regulatory response to the lipoprotein.