Liver cells and lipoproteins

The liver plays a central regulatory role in ·the metabolism of sugars, proteins and lipids. In contrast with sugars, lipids have to be complexed with proteins to socalled lipoproteins before they can be transported in the blood. According to their density, which is determined by the lipid-protein ratio, the lipoproteins can be divided into 4 subclasses; chylomicrons, very low-density lipoproteins (VLDL), low-density lipoproteins (LDL) and high-density lipoproteins (HDL). Studies on the relation between the incidence of coronary artery disease (CAD) and the level of the various lipoproteins in the blood have indicated that an increased LDL-level in the blood leads to a higher risk. LDL is formed in the blood from VLDL which is synthesized in the liver. The liver is also an important organ for the degradation of LDL. The uptake of LDL from the blood by the liver, forms the subject of this thesis. The four major cell types present in the liver are; the parenchymal, the endothelial, the Kupffer and the fat-storing cells. The parenchymal cells contribute 92.5% to totallivermass. Although the non-parenchymal cells contribute only 7,5% it was suggested that these cell types could play an important role in the degradation of LDL. Before the interaction between LDL and the different liver cell types could be studied it was necessary to develop a cell isolation procedure that results in pure intact cells (appendixpaper II). An additional result of the search for a suitable isolation procedure was the discovery of particles (blebs) derived from parenchymal cells with a size similar as non-parenchymal cells. By standard cell isolation procedures these blebs are co-isolated with the non-parenchymal cells unless appropriate precautions are taken