Activation of monocytes in vivo causes intracellular accumulation of lipoprotein-derived lipids and marked hypocholesterolemia - a possible pathogenesis of necrobiotic xanthogranuloma

Necrobiotic xanthogranuloma (NXG) is a rare histiocytic disease with genera lized xanthomatosis. However, most cases with NXG are normolipidemic or hyp olipidemic. The mechanism for the formation of xanthoma in NXG has not yet been clarified. We observed a case of NXG with severe hypocholesterolemia ( total cholesterol: 1.69 mmol/l) and analyzed the function of monocytes in t his case. Histological examinations by light microscopy revealed a large am ount of lipid deposition in the patient's freshly isolated monocytes. The p atient's monocytes showed a 3-fold increase in cholesteryl ester content an d a 3-fold enhancement of acetyl low density lipoprotein (LDL) uptake compa red with the control monocytes. However, no significant difference was note d in the expression of CD36 protein and the mRNA levels of scavenger recept or-class A (SR-A) between the monocytes of the patient and the control. The phagocytotic ability of the patient's monocytes was enhanced 1.5-fold comp ared with that of the control monocytes. These findings suggest that the ac tivated monocytes may have degraded the modified LDL via a pathway other th an CD36 or SR-A, and accumulated a great amount of lipids in vivo. In concl usion, the present study has demonstrated a possible pathogenesis of NXG th at the activation of monocytes in vivo may contribute to the intracellular accumulation of lipoprotein-derived lipids leading to non-inherited xanthom atosis and the marked hypocholesterolemia. (C) 1999 Elsevier Science Inland Ltd. All rights reserved.