Factors regulating the metabolism of low-density lipoprotein-proteoglycan complex in macrophages

Abstract

We studied the factors regulating the metabolism of low-density lipoprotein (LDL)-proteoglycan complex, LDL and acetyl-LDL in mouse peritoneal macrophages. Macrophage conditioned medium stimulated the degradation of LDL-proteoglycan complex and acetyl-LDL in a dose-dependent manner and enhanced cholesterol ester synthesis mediated by these ligands. The conditioned medium had no such effect in a cell-free system. The conditioned medium enhanced the degradation of both the LDL and proteoglycan components of the complex. The degradation of LDL was not affected by the conditioned medium. The active factor in the conditioned medium was labile to boiling, suggesting that it may be protein in nature. The conditioned medium also lost its stimulatory activity after dialysis through a membrane with an exclusion limit of 25000 daltons, suggesting the involvement of cytokines and/or other growth factors. Macrophage activation was accompanied by a 2–3-fold increase in the degradation of LDL-proteoglycan complex and acetyl-LDL as compared to the degradation of these ligands in resident macrophages; however, this had no effect on LDL degradation. The degradation of all three ligands increased markedly with decreasing cell density. Preincubation of macrophages for 48 h with increasing concentrations of fetal bovine serum produced a substantial increase in the subsequent degradation of LDL-proteoglycan complex and acetyl-LDL, while it had very little effect on the degradation of LDL. The active factor in serum was destroyed by boiling, suggesting that it may be a protein. These results show that the scavenger receptor, mediating the uptake and degradation of LDL-proteoglycan complex and acetyl-LDL and LDL receptor are regulated differently in mouse peritoneal macrophages.