Modified LDLs are internalized by macrophages in part via macropinocytosis.
Macrophage foam cell formation in vitro requires uptake of modified low density lipoproteins (LDL) such as acetylated LDL (AcLDL) and moderately oxidized LDL (OxLDL). Macrophages incubated with AcLDL and OxLDL, but not LDL, showed increased membrane ruffling as seen with time-lapse phase contrast video light microscopy. Modified LDLs stimulated circular membrane ruffles between 2 and 10 min after incubation. These membrane ruffles were readsorbed into the plasma membrane between 5 and 15 min later. Phase-bright macropinosomes formed at the base of the stimulated membrane ruffles. The fluid-phase marker lucifer yellow labeled the modified LDL stimulated macropinosomes. Modified LDLs stimulate fluid-phase uptake by 1.5-fold to threefold as measured with 14C-sucrose uptake. Transmission electron microscopy showed that gold conjugated AcLDL and OxLDL bound preferentially to membrane ruffles and were present in macropinosomes (diameter >0.2 pm) underneath these membrane ruffles. AcLDL and OxLDL were also present in clathrin-coated pits and endosomes. These studies suggest that modified lipoproteins stimulate macropinocytosis. AcLDL and OxLDL are partially internalized by macropinocytosis and partially internalized via clathrin-coated pit endocytosis.
D000818:Animals; D002478:Cells, Cultured; D010856:Columbidae; D005487:Foam Cells / Q000502:physiology*; D007546:Isoquinolines; D008077:Lipoproteins, LDL; D008856:Microscopy, Fluorescence; D008858:Microscopy, Phase-Contrast; D009000:Monocytes / Q000502:physiology; D010873:Pinocytosis; D013997:Time Factors