Contribution of xanthoma tissue-derived LDL density substances in the transformation of macrophages to foam cells

Summary Background The source of accumulated lipids in the foam cells of xanthoma is primarily the lipoproteins existing in the lesional dermis. Objective This study was designated to clarify the contribution of low density lipoprotein (LDL) density substances existing in xanthoma tissue to foam cell formation. Methods An LDL density fraction was obtained from homogenized rabbit experimental xanthoma tissue. Biochemical and functional characteristics of xanthoma-extracted LDL density substance were examined. The in vivo foam cell-inducing ability of xanthoma-extracted LDL density substance was examined microscopically at the intradermal injection site. Results Xanthoma-extracted LDL density substance showed more negatively charged mobility on agarose gel electrophoresis than plasma native LDL. A small amount of aggregated material remained at the origin on agarose gel electrophoresis. Xanthoma-extracted LDL density substance contained much higher level of lipid peroxides than native LDL. Mouse peritoneal macrophages internalized xanthoma-extracted LDL density substance extensively and transformed into foam cells by incubation with xanthoma-extracted LDL density substance. Intradermal injection of the xanthoma-extracted LDL density substance induced foam cell infiltration in the skin of a normolipemic rabbit. Conclusion LDL density substances prepared ex vivo from experimental xanthoma tissue contained lipid–protein complexes that have physiochemical properties of oxidized LDL. The lipid–protein complexes were incorporated into foam cells. The substances were considered to contribute to foam cell recruitment during the persistence of xanthoma lesions.