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
P. Holvoet et al., 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, The Journal of clinical investigation, 93(1), 1994, pp. 89-98
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.