Interaction of LDL with human arterial proteoglycans stimulates its uptake by human monocyte-derived macrophages.
The aim of this work was to investigate the possible mechanisms for uptake by human monocyte-derived macrophages (HMDM) of low density lipoprotein (LDL) pretreated with human arterial chondroitin-6-SO4-rich proteoglycan (LDL-PG). HMDM were incubated with 125I-labeled tyramine cellobiose-labeled LDL-PG, native LDL, and acetylated LDL (Ac-LDL). The results showed that two to four times more LDL-PG than LDL was bound and internalized by the HMDM. Competition experiments showed that LDL-PG competed with native LDL for the apoB,E (LDL) receptor, but not for the Ac-LDL scavenger receptor. Both the LDL and LDL-PG uptake were reduced after preincubation of the macrophages with unlabeled native LDL, though to a lesser extent with LDL-PG. The specific binding of 125I-labeled LDL and 125I-labeled LDL-PG at 4 degrees C was both saturable and concentration-dependent. The dissociation constant (Kd) for binding was 8.6 x 10(-9) M for LDL and 9.4 x 10(-9) M for LDL-PG, but the maximum binding (Bmax) was 1.5-times higher for LDL-PG. Cholesterol derived from LDL-PG was less effective than native LDL in suppressing HMG-CoA reductase activity. The results indicate that the uptake of LDL-PG is mediated not only by the LDL-receptor, but also by another unspecific pathway, which may not be subjected to regulation. These results provide further support for the hypothesis that LDL modifications induced by arterial PG may contribute to the formation of foam cells.
Hurt
E
E
Wallenberg Laboratory for Cardiovascular Research, University of Göteborg, Sahlgren's Hospital, Sweden.
Bondjers
G
G
Camejo
G
G
D000107:Acetylation; D001011:Aorta / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D002809:Chondroitin Sulfates; D002850:Chromatography, Gel; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D008074:Lipoproteins / Q000097:blood / Q000172:deficiency; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D011485:Protein Binding; D011509:Proteoglycans / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism
D008074:Lipoproteins; D008077:Lipoproteins, LDL; D011509:Proteoglycans; D011973:Receptors, LDL; D002809:Chondroitin Sulfates; D006903:Hydroxymethylglutaryl CoA Reductases