Summary
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 indistiguishable 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.
Keywords
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Alving CR (1986) Antibodies to liposomes, phospholipids, and phosphate esters. Chem Phys Lipids 40:303–314
Alving, CR, (1990) Antibodies to liposomes, phospholipids, and cholesterol: Implications for autoimmunity, atherosclerosis, and aging. In: Nicholau C, Chapman D (eds) Horizons in Membrane Biotechnology A R Liss, New York 41–51
Alving CR, Swartz Jr GM (1991) Antibodies to cholesterol, cholesterol conjugates, and liposomes: Implications for atherosclerosis and autoimmunity. CRC Crit Rev Immunol 10:441–453
Alving CR, Swartz Jr GM, Wassef NM (1989) Naturally-occurring autoantibodies to cholesterol in humans. Biochem Soc Trans 17:637–639
Alving CR, Swartz Jr GM, Wassef NM, Herderick EE, Virmani R, Kolodgie FD, Matyas GR, Ribas JL, Kenner JR, Cornhill JF (1995a) Vaccination against cholesterol: immunologic modulation of diet-induced hypercholesterolemia and atherosclerosis. In: Woodford P, Davignon J, Sniderman A (eds) Atherosclerosis X Elsevier Science BV, Amsterdam 944–948
Alving CR, Swartz Jr GM, Wassef NM, Herderick EE, Virmani R, Kolodgie FD, Matyas GR, Ribas JL, Kenner JR, Cornhill JF (1995b) Prospects for an anti-cholesterol vaccine. Clin Immunother 3:409–414
Banerji B, Lyon JA, Alving CR (1982) Membrane lipid composition modulates the binding specificity of a monoclonal antibody against liposomes. Biochim Biophys Acta 689:319–326
Bauer BJ, Blashfield K, Norris R, Buthala DA, Ginsberg LC (1982) Immunoglobulin as the major low density lipoprotein binding protein in plasma. Atherosclerosis 44:153–160
Fogler WE, Swartz Jr GM, Alving CR (1987) Antibodies to phospholipids and liposomes: Binding of antibodies to cells. Biochim Biophys Acta 903:265–272
Grant CWM (1986) Model membranes bearing glycolipids and glycoproteins. Chem Phys Lipids 40:285–302
Koscielak J. Hakomori S, Jeanloz RW (1968) Glycolipid antigen and its antibody. Immunochemistry 5:441-445
Nairn JO, Lanzafame RJ (1993) The adjuvant effect of silicone-gel on antibody formation in rats. Immunol Invest 22:151–161
Pal R, Barenholz Y, Wagner RR (1980) Effect of cholesterol concentration on organization of viral and vesicle membranes. J Biol Chem 225:5802–5806
Potter M, Morrison S, Wiener F, Xiaokui KZ, Miller FW (1994) Induction of plasmacytomas with silicone gel in genetically susceptible strains of mice. J Cancer Natl Inst 86:1058–1065
Schuster B, Neidig M, Alving BM, Alving CR (1979) Production of antibodies against phosphocholine, phosphatidylcholine, sphingomyelin, and lipid A by injection of liposomes containing lipid A. J. Immunol 122:900–905
Shichijo S, Alving CR (1985) Influence of glycolipids on immune reactions of phospholipid antigens in liposomes. Biochim Biophys Acta 820:289–294
Shichijo S, Alving CR (1986) Inhibitory effects of gangliosides on immune reactions of antibodies to neutral glycolipids in liposomes. Biochim Biophys Acta 858:18–124
Swartz Jr GM, Gentry MK, Amende LM, Blanchette-Mackie, EJ, Alving CR (1988) Antibodies to cholesterol. Proc Natl Acad Sci USA 85:1902–1906
Wassef NM, Roerdink F, Swartz Jr GM, Lyon JA, Berson, B.J., Alving, CR. (1984) Phosphate binding specificities of monoclonal antibodies against phosphoinositides in liposomes. Mol Immunol 21:863–868
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1996 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Alving, C.R., Wassef, N.M., Potter, M. (1996). Antibodies to Cholesterol: Biological Implications of Antibodies to Lipids. In: Potter, M., Rose, N.R. (eds) Immunology of Silicones. Current Topics in Microbiology and Immunology, vol 210. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-85226-8_18
Download citation
DOI: https://doi.org/10.1007/978-3-642-85226-8_18
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-85228-2
Online ISBN: 978-3-642-85226-8
eBook Packages: Springer Book Archive