Process and characterization of LDL modified to be incorporated into macrophages

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Xanthoma develops by the infiltration of lipid-laden foam cells similarly to atherosclerosis. To clarify the precise processes of foam cell infiltrating lesions, xanthoma is more competent than atherosclerosis in the visual inspection and taking the lesional specimens. The following results were obtained by using rabbit experimental xanthoma tissues. 1) From the experimental xanthoma tissues, more negatively charged LDL than native LDL was obtained and it was revealed to transform macrophages to foam cells. These cationized lipoproteins may contribute to the recruitment of foam cells in xanthoma tissues. 2) Human LDL was made more negatively charged and contained a larger amount of lipid peroxides than native LDL by incubation with experimental xanthoma tissues that were made by intradermal injections of carrageenan on diet -induced hypercholesterolemic rabbits. Mouse peritoneal macrophages incorporated more oxidized LDL than native LDL and the macrophages transformed to foam cells. Th … More e oxidization was inhibited by several antioxidants, for instance superoxide dismutase, butylated hydroxytoluene, alpha-tocopherol and catalase. No different inhibitory effects were observed among these antioxidants. These findings indicate that extravasated LDL is oxidatively modified and contributes to foam cell formation in xanthoma tissues. However, the precise mechanisms of the oxidization were not revealed. 3) Intradermal injections of hyaluronic acid induced infiltration of foam cells on hypercholesterolemic rabbits . Hyaluronic acid formed soluble complexes in vitro with lipoproteins of human whole serum and also with isolated LDL and VLDL of hypercholesterolemic rabbits. Extravasated LDL and VLDL might form soluble complexes with hyaluronic acid and receive oxidative modification in the dermis. It was suggested that the oxidized lipoproteins induced infiltration of macrophages and the macrophages transformed to foam cells by incorporating the oxidized lipoproteins. 4) The studies on the following subjects have to be continued: a)expression of monocyte adhesion molecules on the endothelial cells by the LDL modified by incubation with the experimental xanthoma tissues, 2)characterization of apolipoproteins and lipid moieties of lipoproteins that have been modified by the experimental xanthoma tissues. Less