Process and characterization of LDL modified to be incorporated into macrophages

黄瘤是由富含脂质的泡沫细胞渗透而成，类似于动脉粥样硬化。为了阐明泡沫细胞浸润性病变的确切过程，在肉眼检查和取皮损标本方面，黄色瘤比动脉粥样硬化更准确。以兔实验性黄瘤组织为研究对象，获得了以下结果。1)从实验性黄瘤组织中，可获得比天然低密度脂蛋白更多的负电荷低密度脂蛋白，并可将巨噬细胞转化为泡沫细胞。这些阳离子脂蛋白可能有助于黄瘤组织中泡沫细胞的募集。2)在饮食诱导的高胆固醇血症兔皮内注射角叉菜胶制成的实验性黄瘤组织与人低密度脂蛋白孵育后，人低密度脂蛋白比天然低密度脂蛋白带更多的负电荷，并含有更多的过氧化脂质。小鼠腹腔巨噬细胞比天然低密度脂蛋白吸收更多的氧化低密度脂蛋白，巨噬细胞转化为泡沫细胞。TH…几种抗氧化剂如超氧化物歧化酶、丁基羟基甲苯、α-生育酚和过氧化氢酶可抑制更多的e氧化。这些抗氧化剂之间没有不同的抑制作用。这些发现表明，渗出的低密度脂蛋白是氧化修饰的，有助于黄瘤组织中泡沫细胞的形成。然而，氧化的确切机制并未被揭示。3)皮内注射透明质酸可诱导高胆固醇血症兔泡沫细胞的渗出。透明质酸在体外与人全血清脂蛋白、高胆固醇血症兔分离的低密度脂蛋白和极低密度脂蛋白形成可溶性络合物。渗出的低密度脂蛋白和极低密度脂蛋白可能与透明质酸形成可溶的络合物，并在真皮中接受氧化修饰。提示氧化型脂蛋白可诱导巨噬细胞的渗入，巨噬细胞通过掺入氧化型脂蛋白而转化为泡沫细胞。4)实验黄瘤组织温育修饰的低密度脂蛋白对内皮细胞表达单核细胞黏附分子的影响；2)实验黄瘤组织修饰的载脂蛋白及其脂类成分的特性。较少

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