AUTOANTIBODIES TO RIBOSOMAL-P PROTEINS PENETRATE INTO LIVE HEPATOCYTES AND CAUSE CELLULAR DYSFUNCTION IN CULTURE

Abs to ribosomal P protein have been shown to bind a membrane form of the P-0 38-kDa ribosomal phosphoprotein. This study shows that after a ffinity-purified Abs to ribosomal P proteins bind living HepGZ cells, they then penetrate these live cells and cause cellular dysfunction. B inding and penetration of anti-P Abs is the property of F(ab')(2) frag ments as well as whole IgG molecules showing that neither binding nor penetration depends on Fc fragments or their cognate receptors. Confoc al microscopy shows that internalized Ab concentrates in perinuclear v esicles (presumably lysosomes), but substantial quantities of Ab are a lso found in the cytosol. This intracellular Ab adversely affects the synthesis of apolipoprotein B resulting in a threefold increase in cel lular cholesterol with lipid droplet accumulation as seen in some chro nic liver diseases. It also has a profound inhibitory effect on global protein synthesis as measured by [(35)]methionine incorporation. Thes e studies therefore describe a model of cellular injury effected by sp ecific Ab to ribosomal ''P'' protein that may underlie certain forms o f autoimmune hepatic diseases.