ENHANCED LOW-DENSITY-LIPOPROTEIN DEGRADATION AND CHOLESTEROL-SYNTHESIS IN MONOCYTE-DERIVED MACROPHAGES OF PATIENTS WITH ADULT XANTHOGRANULOMATOSIS

Adult xanthogranulomatosis is an uncommon disorder in which dermal mac rophages accumulate cholesterol intracellularly despite normal plasma cholesterol levels. In an attempt to elucidate an underlying biochemic al abnormality in this disorder, we studied the rates of I-125-labeled low-density lipoprotein degradation, and intracellular cholesterol sy nthesis, in human monocyte-derived macrophages of three patients with adult xanthogranulomatosis. In all three patients, the rates of cellul ar I-125-low-density lipoprotein degradation and of cholesterol synthe sis were 22-37% and 14-84% higher than those of the respective normal controls (p < 0.01). These findings suggest that in MDM of adult xanth ogranulomatosis patients, the uptake and degradation of low-density li poprotein-derived cholesterol and intracellular cholesterol biosynthes is are enhanced. Because derma macrophages are derived from blood mono cytes, it is possible that such an enhancement might play a role in th e accumulation of cholesteryl esters in the macrophages that form the xanthogranulomatosis lesions.