Immunoglobulin G, F(AB')2, and fab fragment uptake kinetics in isolated perfused rat liver and rat hepatic cells.
The interaction of 125I-radiolabeled immunoglobulin G (IgG), F(ab')2, and Fab fragments with different modes of production (polyclonal or monoclonal), belonging to different subclasses (IgG1 and IgGT) and derived from different sources (mouse, rat, and horse) with liver, was investigated by using isolated perfused rat liver and isolated rat hepatic parenchymal cells (PCs) and non-parenchymal cells (NPCs) in suspension. Lactosaminated-bovine serum albumin (Lac-BSA) and formaldehyde-bovine serum albumin were used as markers of specific binding to PCs and NPCs, respectively. Using the isolated perfused rat liver model, data clearly indicated a very weak hepatic extraction ratio (< 0.003) for IgGs and fragments in comparison with Lac-BSA (extraction ratio = 0.398) over the 3 hr of the experiments. No breakdown or higher molecular weight compounds were observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. Biliary excretion of IgGs and fragments ranged from 0.07 to 0.3%, mainly as free iodine-125. In contrast, 7% of Lac-BSA was excreted unchanged in bile, and 10% of free iodine was excreted at 3 hr. In vitro binding studies showed no specific binding of any antibody and fragment proteins at 4 degrees C or 37 degrees C. In contrast, saturable uptake was observed for Lac-BSA with PCs and formaldehyde-bovine serum albumin with NPCs. Both models demonstrated that nonspecific antibody/fragment interactions occurred with rat liver. Several hypotheses can be formulated to explain why liver-antibody interactions depend on more complex antibody molecular states (aggregated structure and immune complex) rather than the monomeric structure investigated in the present study.
Bazin-Redureau
M
M
INSERM U26, Paris, France.
Gires
P
P
Chapelle
P
P
Martinet
M
M
Scherrmann
J M
JM
D000818:Animals; D001646:Bile / Q000378:metabolism; D006207:Half-Life; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley
D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes