IMMUNOGLOBULIN-G, F(AB')(2), AND FAB FRAGMENT UPTAKE KINETICS IN ISOLATED-PERFUSED RAT-LIVER AND RAT HEPATIC CELLS

The interaction of I-125-radiolabeled immunoglobulin G (IgG), F(ab')(2 ), and Fab fragments with different modes of production (polyclonal or monoclonal), belonging to different subclasses (IgG(1) and IgG(T)) an d derived from different sources (mouse, rat, and horse) with liver, w as investigated by using isolated perfused rat liver and isolated rat hepatic parenchymal cells (PCs) and nonparenchymal cells (NPCs) in sus pension, Lactosaminated-bovine serum albumin (Lac-BSA) and formaldehyd e-bovine serum albumin were used as markers of specific binding to PCs and NPCs, respectively, Using the isolated perfused rat liver model, date clearly indicated a very weak hepatic extraction ratio (<0.003) f or IgGs and fragments in comparison with Lac-BSA (extraction ratio = 0 .398) over the 3 hr of the experiments. No breakdown or higher molecul ar weight compounds were observed by sodium dodecyl sulfate-polyacryla mide gel electrophoresis analysis, Biliary excretion of IgGs and fragm ents 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 bind ing 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 an d formaldehyde-bovine serum albumin with NPCs, Both models demonstrate d that nonspecific antibody/fragment interactions occurred with rat li ver, Several hypotheses can be formulated to explain why liver-antibod y interactions depend on more complex antibody molecular states (aggre gated structure and immune complex) rather than the monomeric structur e investigated in the present study.