The interaction of carbamylated low-density lipoprotein with cultured cells. Studies with human fibroblasts, rat peritoneal macrophages and human monocyte-derived macrophages.
We determined the effects of various degrees of chemical modification of low-density lipoprotein (LDL) on its interaction with receptors present on human fibroblasts, human monocyte-derived macrophages and rat peritoneal macrophages. We isolated LDL (d = 1.019-1.063 g/ml) and carbamylated different numbers of lysine residues and tested its cell-interactive properties, including binding, degradation, and stimulation of [3H]oleate incorporation into cholesteryl oleate. Small carbamylation of LDL (approximately 1-2% of lysine residues) resulted in a reduced ability (70-80% of control) to displace 125I-labeled LDL from fibroblast receptors. Modification of 12.5-25% of lysine residues resulted in a marked increase in the ability of LDL to interact with scavenger receptors and an almost total loss in the ability to interact with apolipoprotein B-E receptors. Acetylated LDL and malondialdehyde-modified LDL inhibited competitively the degradation of 125I-carbamylated LDL by human macrophages. Thus, the extent of modification plays an important role in recognition of modified LDL by scavenger receptors. There also seems to be a range of modification over which LDL is not yet recognized by the scavenger receptor, but its interaction with the apolipoprotein B-E receptor is markedly reduced. This perhaps explains how a small in vivo modification of LDL can result in an increase in residence time of LDL in the subendothelial tissue which can lead to further local interactions, ultimately increasing the atherogenicity of the LDL particle.
D000818:Animals; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D011973:Receptors, LDL
D008077:Lipoproteins, LDL; D011956:Receptors, Cell Surface; D011973:Receptors, LDL; C039916:carbamyl-LDL