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 P0 38-kDa ribosomal phosphoprotein. This study shows that after affinity-purified Abs to ribosomal P proteins bind living HepG2 cells, they then penetrate these live cells and cause cellular dysfunction. Binding and penetration of anti-P Abs is the property of F(ab')2 fragments as well as whole IgG molecules showing that neither binding nor penetration depends on Fc fragments or their cognate receptors. Confocal microscopy shows that internalized Ab concentrates in perinuclear vesicles (presumably lysosomes), but substantial quantities of Ab are also found in the cytosol. This intracellular Ab adversely affects the synthesis of apolipoprotein B resulting in a threefold increase in cellular cholesterol with lipid droplet accumulation as seen in some chronic liver diseases. It also has a profound inhibitory effect on global protein synthesis as measured by [35S]methionine incorporation. These studies therefore describe a model of cellular injury effected by specific Ab to ribosomal "P" protein that may underlie certain forms of autoimmune hepatic diseases.
Koscec
M
M
Arthritis/Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
Koren
E
E
Wolfson-Reichlin
M
M
Fugate
R D
RD
Trieu
E
E
Targoff
I N
IN
Reichlin
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000974:Antibodies, Antinuclear / Q000378:metabolism; D001055:Apolipoproteins B / Q000096:biosynthesis; D001323:Autoantibodies / Q000378:metabolism* / Q000633:toxicity; D008099:Liver / Q000378:metabolism*; D008969:Molecular Sequence Data; D015800:Protozoan Proteins; D051381:Rats; D012269:Ribosomal Proteins / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000974:Antibodies, Antinuclear; D001055:Apolipoproteins B; D001323:Autoantibodies; C064601:L12E protein, Trypanosoma cruzi; D015800:Protozoan Proteins; D012269:Ribosomal Proteins