CHARACTERIZATION OF THE BINDING OF LOW-DENSITY LIPOPROTEINS TO CULTURED RAT MESANGIAL CELLS

Mesangial cell lipid accumulation is a recognised feature of glomerular disease and has been implicated as a factor in the pathogenesis of renal injury. To investigate possible mechanisms of such accumulation, binding of I-125-labelled human low-density lipoprotein (LDL) to rat mesangial cells was studied in vitro. Experiments were performed at 4-degrees-C to prevent ligand internalisation. LDL remained associated with the cells after repeated washing. Binding was time-dependent, was inhibited by addition of an excess of unlabelled LDL, but to a much lesser extent by apoprotein-A-rich high-density lipoprotein particles devoid of apoprotein E (HDL-A). Specific binding reached saturation at an LDL concentration of 21-mu-g/ml, required the presence of calcium, and was inhibited by heparin and dextran sulphate. Scatchard analysis suggested a single class of binding site (Kd 22.7-mu-g protein/ml). Higher binding affinities were obtained when rat LDL was substituted for human LDL (Kd 1.3-mu-g/ml) and when human fibroblasts were exposed to human LDL under identical experimental conditions (Kd 3.0-mu-g/ml). Further experiments at 37-degrees-C demonstrated degradation of LDL by cells. These results suggest that mesangial cells possess apoprotein B, E receptors. Mesangial cell lipid accumulation may therefore result from receptor-mediated endocytosis of LDL particles.