Specificity of receptor-mediated re modified low density lipoproteins (scavenger receptor/low density lipoprotein receptor/human monoc

Blood-borne human monocytes and macro- phages derived from human monocytes in vitro express an active low density lipoprotein (LDL) receptor and an active receptor for negatively charged proteins, the scavenger receptor. When < 15% of the lysine residues of human LDL were modified by malondi- aldehyde while the lipoprotein was in solution, recognition and uptake of the modified lipoprotein occurred via the LDL receptor. Further modification resulted in threshold recognition and uptake by the scavenger receptor with concomitant loss of recognition by the LDL receptor. The rate of degradation via the LDL receptor pathway was inversely related to the degree of modification whereas that mediated by the scavenger receptor was indepen- dent of the extent of incorporation of malondialdehyde once threshold recognition was achieved. In contrast to the interaction of LDL with malondialdehyde in solution, modification of <15% of the lysine residues of LDL adsorbed to heparin-Sepharose re- sulted in recognition and uptake by the scavenger receptor. The scavenger receptor-mediated uptake of malondialdehyde-modi- fied LDL may be dependent on formation of recognition sites in- volving specific modified lysine residues or changes in the con- formation of LDL induced by neutralization of specific lysine residues of the apoB polypeptides or both.