Antibodies to cholesterol.
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.
Swartz
G M
GM
Department of Membrane Biochemistry, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Gentry
M K
MK
Amende
L M
LM
Blanchette-Mackie
E J
EJ
Alving
C R
CR
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
D000911:Antibodies, Monoclonal; D008050:Lipid A; D008081:Liposomes; D002784:Cholesterol