title: Antibodies to cholesterol.
abstract: Cholesterol-dependent complement activation has been proposed as a factor that might influence the pathogenesis of atherosclerosis. Although antibodies to cholesterol conjugates have been reported, cholesterol is widely regarded as a poorly immunogenic substance. Monoclonal IgM complement-fixing antibodies to cholesterol were obtained in the present study after immunizing mice with liposomes containing high amounts of cholesterol (71 mol % relative to phosphatidylcholine) and lipid A as an adjuvant. Clones were selected for the ability of secreted antibodies to react with liposomes containing 71% cholesterol but not with liposomes containing 43% cholesterol. The antibodies also reacted with crystalline cholesterol in a solid-phase enzyme-linked immunosorbent assay. Binding of monoclonal antibodies to the surface of crystalline cholesterol was demonstrated by electron microscopy by utilizing a second antibody (anti-IgM) labeled with colloidal gold. The immunization period required to induce monoclonal antibodies was very short (3 days) and a high fraction of the hybrid cells (at least 70%) were secreting detectable antibodies to cholesterol. The results demonstrate that cholesterol can be a highly immunogenic molecule and that complement-fixing antibodies to cholesterol can be readily obtained.
authors.affiliation: Department of Membrane Biochemistry, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
authors.forename: G M
authors.initials: GM
authors.lastname: Swartz
authors.forename: M K
authors.initials: MK
authors.lastname: Gentry
authors.forename: L M
authors.initials: LM
authors.lastname: Amende
authors.forename: E J
authors.initials: EJ
authors.lastname: Blanchette-Mackie
authors.forename: C R
authors.initials: CR
authors.lastname: Alving
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D002784:Cholesterol / Q000276:immunology*; D003460:Crystallization; D004797:Enzyme-Linked Immunosorbent Assay; D008050:Lipid A; D008081:Liposomes; D051379:Mice; D008854:Microscopy, Electron
chemical_list: D000911:Antibodies, Monoclonal; D008050:Lipid A; D008081:Liposomes; D002784:Cholesterol