Alving C R, Wassef N M, Potter M
Department of Membrane Biochemistry, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.
Curr Top Microbiol Immunol. 1996;210:181-6. doi: 10.1007/978-3-642-85226-8_18.
Injection of silicone gel or silicone oil intraperitoneally into BALB/c mice induced the formation of antibodies that reacted by ELISA with highly purified crystalline cholesterol and, to a much lesser extent, antibodies that reacted with a phospholipid (dimyristoyl phosphatidylglycerol). Although IgM and IgG antibodies to cholesterol were detected, the titers of IgG antibodies were low when compared with IgM. The titers of IgM antibodies to cholesterol in certain sera exhibited activities that reached baseline values at dilutions as high as 1:5000, thus making them equivalent to titers that have been previously published for ascites fluid containing murine monoclonal antibodies to cholesterol. The antibodies to cholesterol induced by silicone compounds are indistinguishable in their binding to crystalline cholesterol from naturally-occurring antibodies to cholesterol in normal human serum. They are also indistinguishable from antibodies induced by a proposed vaccine to cholesterol that is currently in late preclinical development for prevention of hypercholesterolemia in humans. The anti-cholesterol vaccine, which consists of liposomes heavily laden with cholesterol as an antigen and lipid A as an adjuvant, induces antibodies that react with low density lipoproteins (LDL) and opsonize them for removal by liver macrophages. It appears that silicone gel or silicone oil causes recruitment and adsorption of cholesterol at the injection site, and also serves as an adjuvant that may have immunostimulant properties similar to lipid A for inducing antibodies to lipids. Antibodies to lipids such as cholesterol or phospholipids are not harmful to intact cell membranes because of steric hindrance from surrounding lipids and larger macromolecules that block binding of the antibodies.
向BALB/c小鼠腹腔内注射硅胶或硅油可诱导抗体形成，这些抗体通过酶联免疫吸附测定（ELISA）与高度纯化的结晶胆固醇发生反应，与磷脂（二肉豆蔻酰磷脂酰甘油）发生反应的抗体则少得多。虽然检测到了针对胆固醇的IgM和IgG抗体，但与IgM相比，IgG抗体的效价较低。某些血清中针对胆固醇的IgM抗体效价在高达1:5000的稀释度时仍表现出活性，因此与先前发表的含有鼠抗胆固醇单克隆抗体的腹水效价相当。由硅化合物诱导产生的抗胆固醇抗体，在与结晶胆固醇结合方面，与正常人血清中天然存在的抗胆固醇抗体没有区别。它们也与一种正在进行临床前后期开发、用于预防人类高胆固醇血症的胆固醇疫苗诱导产生的抗体没有区别。这种抗胆固醇疫苗由富含胆固醇作为抗原的脂质体和作为佐剂的脂多糖A组成，可诱导与低密度脂蛋白（LDL）发生反应的抗体，并使其被肝巨噬细胞清除。似乎硅胶或硅油会在注射部位募集和吸附胆固醇，并且还作为一种佐剂，可能具有与脂多糖A类似的免疫刺激特性，用于诱导针对脂质的抗体。针对胆固醇或磷脂等脂质的抗体，由于周围脂质和较大的大分子的空间位阻作用，阻止了抗体的结合，因此对完整的细胞膜无害。
