INTERACTION OF ANTI-CHOLESTEROL ANTIBODIES WITH HUMAN LIPOPROTEINS

Inoculation of mice with cholesterol-rich liposomes containing the adj uvant monophosphoryl lipid A results in the production of antiserum co ntaining IgM Ab to cholesterol. The specificity of the Ab was to chole sterol and structurally similar sterols containing a 3 beta-hydroxyl g roup. Anti-cholesterol binding activity was significantly diminished i f the 3 beta-hydroxyl was altered by either epimerization, substitutio n, oxidation, or esterification. A similar specificity for 3 beta-hydr oxy-sterols was observed for an anti-cholesterol IgM mAb. Both hyperim mune serum and the mAb reacted with intact human very-low-/intermediat e-density lipoprotein (VLDL/IDL) and low-density lipoproteins (LDL), b ut not high-density lipoproteins (HDL), in an ELISA, but could react w ith total lipid extracts containing cholesterol that were prepared fro m all three lipoprotein classes. Functionally, immune serum or the mAb aggregated and induced a fusion-like reaction with VLDL/IDL and LDL a t low temperatures: these aggregates result in spherical structures vi sible with light microscopy. Similarly, binding of anti-cholesterol Ab to small cholesterol-rich liposomes resulted in the appearance of ves icular structures with approximately 20- to 200-fold increased diamete rs. These data demonstrate that the anti-cholesterol Ab recognize unes terified cholesterol in VLDL/IDL and LDL; high-density lipoprotein cho lesterol in the intact lipoprotein, however, appears to be protected f rom reaction with these Ab.