Alterations in plasma clearance and tissue localization of model immune complexes in rats with streptozotocin-induced...

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.