STIMULATION WITH A MONOCLONAL-ANTIBODY (MAB4E4) OF SCAVENGER RECEPTOR-MEDIATED UPTAKE OF CHEMICALLY-MODIFIED LOW-DENSITY LIPOPROTEINS BY THP-1-DERIVED MACROPHAGES ENHANCES FOAM CELL GENERATION

mAb4E4, a murine monoclonal antibody that is specific for acetylated L DL and malondialdehyde-treated LDL, binds specifically to modified LDI , present in human atherosclerotic lesions. It is directed against an epitope that is poorly exposed in delipidated and solubilized apolipop rotein B-100 from modified LDL. mAb4E4, as well as its P(ab')(2) and F ab fragments, enhanced the uptake of both acetylated LDL and malondial dehyde-treated LDL by THP-I-derived macrophages resulting in a sixfold increase of cytoplasmic cholesteryl ester levels. The increased uptak e of modified LDL/mAb4E4 complexes did not occur via the Fc receptor a nd did not depend on aggregation of modified LDL particles. However, t heir uptake was inhibited by blocking the scavenger receptors with fuc oidin or by down regulation of receptor expression with endotoxins or interferon-gamma, indicating that their uptake is mediated via these r eceptors. Thus, generation of autoimmune antibodies against modified L DL and subsequent endocytosis of soluble modified LDL/antibody complex es via scavenger receptors may enhance foam cell generation. This mech anism may contribute to the progression of atherosclerotic lesions.