The Influence of Apolipoprotein E on the Interactions between Normal Human Very Low Density Lipoproteins and U937 Human Macrophages: Heterogeneity among Persons

Apolipoprotein E (apo E) can mediate the cell binding of normal human very low density lipoproteins (VLDL). However, the extent to which apo E is involved in the cell binding and uptake of VLDL from different normolipidemic persons is not well defined. The VLDL (d< 1.006 g/I) of eight subjects were fractionated into VLDL with apo E and without apo E using a monoclonal antibody that binds to the LDL receptor recognition region of apo E. VLDL particles that expressed the 1D7 binding region of apo E comprised an average of 34% (range 7–51%) of the VLDL particles. Anti-apo E blocked an average of 43% (range 8–63%) of the binding of unfractionated VLDL to U937 cells. Anti-apo E blocked a similar proportion of binding to U937 cells of three VLDL subfractions of different density ranges (Sf20–60, Sf60–100, Sf100–400). The proportion of the VLDL particles that contained apo E correlated with the extent of uptake of the total VLDL by U937 cells, but not with stimulation by total VLDL of cholesterol ester formation. The binding to cells of VLDL without apo E varied by six-fold among persons, and caused most of the binding of the total VLDL of some subjects. Therefore, normolipidemic VLDL contains particles across its density range that use apo E to bind to U937 macrophages. In some VLDL samples, apo E provides most of the cell binding activity, whereas in others the binding activity occurs by other means.