Process and characterization of LDL modified to be incorporated into macrophages

黄瘤的发展是由充满脂质的泡沫细胞浸润引起的，与动脉粥样硬化相似。为了阐明泡沫细胞浸润病变的确切过程，在肉眼观察和病变标本的获取上，黄色瘤比动脉粥样硬化更有能力。通过使用兔实验性黄色瘤组织获得以下结果。1)从实验性黄瘤组织中，获得了比天然LDL更多的带负电荷的LDL，并且揭示了将巨噬细胞转化为泡沫细胞。这些阳离子化脂蛋白可能有助于黄色瘤组织中泡沫细胞的募集。2)通过与实验性黄瘤组织一起孵育，使人LDL带更多的负电荷，并且含有比天然LDL更大量的脂质过氧化物，所述实验性黄瘤组织是通过在饮食诱导的高胆固醇血症兔上皮内注射角叉菜胶制成的。小鼠腹腔巨噬细胞吸收氧化型LDL比天然LDL多，并转化为泡沫细胞。日 ...更多信息 E氧化被几种抗氧化剂抑制，例如超氧化物歧化酶、丁基化羟基甲苯、α-生育酚和过氧化氢酶。在这些抗氧化剂中没有观察到不同的抑制作用。这些发现表明，渗出的LDL被氧化修饰，并有助于黄色瘤组织中泡沫细胞的形成。然而，氧化的精确机制尚未揭示。3)皮内注射透明质酸诱导高胆固醇血症家兔泡沫细胞浸润。透明质酸在体外与人全血清的脂蛋白以及与高胆固醇血症兔的分离的LDL和VLDL形成可溶性复合物。渗出的LDL和VLDL可能与透明质酸形成可溶性复合物，并在真皮中接受氧化修饰。结果表明，氧化型脂蛋白可诱导巨噬细胞浸润，并使巨噬细胞向泡沫细胞转化。4)必须继续对以下主题进行研究：a）通过与实验性黄瘤组织孵育修饰的LDL在内皮细胞上表达单核细胞粘附分子，2）表征已被实验性黄瘤组织修饰的载脂蛋白和脂蛋白的脂质部分。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