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Investigators studying the transport of macromolecules across mucosal surfaces have noted that techniques involving exogenously labelled macromolecules result in estimation of transport which exceed estimates based on immunochemical methods. The present study tested the possibility that radio-labelled fragments of macromolecules might bind to host proteins resulting in an apparent increase in 'size' of the fragments. Fragments obtained by dialysis of bovine serum albumin (BSA) labelled with tritium gas by Wilzbach method, bound to normal rabbit serum in vitro and in vivo. Binding to BSA exceeded binding to bovine gamma globulin (BGG). Dinitrophenylated BGG was administered by gavage to adult rats; DNP-bearing fragments were identified in their serum and recovered by gel filtration. After radio-labelling, these serum fractions also bound to macromolecular constituents of normal rat serum. These findings suggest that several different fragments of proteins may bind to native serum components. These results may bear upon in vivo observations since it is likely that following intestinal instillation of extrinsically labelled protein, labelled amino acids or small peptides are generated by the digestive process, become absorbed, bind to serum macromolecules and thereby mimic the uptake of macromolecules.

In order to study the in vivo clearance of model immune complexes, radiolabelled aggregated rat gamma globulin (ARG), aggregated human serum albumin (AHSA) and 59Fe-tagged erythrocytes were intravenously injected into control, and insulin-deficient and insulin-treated rats with streptozotocin-induced diabetes. Plasma clearance and organ uptake were measured. The rate of plasma clearance of ARG was studied at trace (18 micrograms) and near-saturating (10 mg) doses. AHSA was cleared slowly from the circulation, and there were no observed differences between the study groups. At trace doses of ARG, plasma clearance was similar in the three animal groups; however, at the higher dose, clearance was significantly slowed in both insulin-deficient and insulin-treated diabetic rats as compared to control animals (P less than 0.01). Organ uptake of AHSA was similar in all study groups. Hepatic uptake at 10 min after injection of ARG was comparable in control and insulin-deficient rats; however, the rate of removal from the liver was significantly slowed in these diabetic rats. Insulin-treated diabetic rats had less hepatic-associated ARG, as compared to the other animals, throughout the study. Splenic uptake of ARG was comparable in both control and insulin-treated animals, but was significantly less in insulin-deficient diabetic animals. These alterations in plasma clearance and tissue localization of ARG in diabetic animals suggest that abnormal phagocytosis may contribute to the elevated levels of circulating immune complexes that have been demonstrated in diabetic subjects.