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Journal of Lipid Research, Vol 37, 1422-1435, Copyright © 1996 by Lipid Research, Inc.

ARTICLES

Characterization of inherited scavenger receptor overexpression and abnormal macrophage phenotype in a normolipidemic subject with planar xanthomas

C Giry, LM Giroux, M Roy, J Davignon and A Minnich
Clinical Research Institute of Montreal, P.Q., Canada.

It is proposed that, in hyperlipidemia, foam cells develop in cutaneous xanthomas from the uptake by the macrophage scavenger receptor (SR) of low density lipoproteins (LDL) that are modified due to increased residence time in plasma. We have observed extensive xanthelasmas and planar xanthomas in the absence of hyperlipidemia in two siblings. In blood monocytes from one sibling, 125I-labeled acetylated LDL (Ac-LDL) degradation and SR mRNA were 4 and 7 times higher, respectively, than in four control subjects. Among monocytes from these five individuals, variation in Ac-LDL degradation was completely accounted for by SR mRNA levels (R2 = 0.98, P < 0.001). Monocyte SR mRNA was induced upon maturation into macrophages during 7 days in culture. Mean monocyte and macrophage SR mRNA values from one sibling and six additional family members were elevated 5- and 4-fold compared to that of 16 control subjects, and elevated monocyte SR mRNA was associated with abnormally high cell-surface expression of SR epitopes. Monocytes from eight of nine family members examined displayed an unusual phenotype characterized by increased adhesion and rapid maturation into large macrophages which overaccumulated lipids. Monocyte-macrophage SR overexpression relative to control persisted even in the absence of autologous serum, consistent with a cellular abnormality. This is the first demonstration of an inherited abnormality in scavenger receptor expression and its occurrence in association with planar xanthomas.
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