Metabolism of modified LDL and foam cell formation in murine macrophage-like RAW 264 cells

The uptake of modified low density lipoprotein (LDL) by arterial macrophage s is a key event in the atherogenesis. We studied 1) the uptake and degrada tion of modified LDL, 2) LDL recognition by specific receptors, and 3) the foam cell formation with murine macrophage-like RAW 264 cells in vitro. The cells took up and degraded effectively I-125-labeled acetylated LDL (Ac-LD L) and aggregated LDL (Aggr-LDL). Also oxidized LDL (Ox-LDL) was taken up b ut it was degraded poorly. The degradation of I-125-Ac-LDL was efficiently competed by both unlabeled Ac-LDL and-Ox-LDL, whereas the degradation of I- 125-Ox-LDL was partially competed by unlabeled Ox-LDL and Aggr-LDL but not at all by unlabeled Ac-LDL. The incubation with increasing concentrations o f Ac-LDL, Aggr-LDL or Ox-LDL resulted in marked foam cell formation in the RAW 264 cells. Ox-LDL was cytotoxic at 500 to 1000 mu g/ml concentrations. The results show that RAW 264 cells have at least two classes of receptors for modified lipoproteins: one that recognizes both Ox-LDL and Ac-LDL, and is similar to the scavenger receptors, and another that recognizes Ox-LDL b ut not Ac-LDL. RAW 264 cells are a convenient model cell line for examining the metabolism of modified lipoproteins, not only that of Ac-LDL but also that of Ox-LDL and Aggr-LDL, and cellular accumulation of lipids derived fr om modified LDL.