Glycation increases the vascular clearance rate of IgG in mice

SUMMARY As elevated levels of glycated IgG have been detected in the plasma of diabetics we have investigated whether glycation of IgG affects its vascular clearance rate, using a mouse model system. Polyclonal mouse IgG was aseptically incubated for 14–19 days with 0.5 m glucose in 0.1 m phosphate buffer (pH7.4) at 37 C, As control, IgG was incubated under identical conditions but with no added glucose. After incubation, both forms were labelled with 125 I and injected intravenously into BALB/c mice. The rate of vascular clearance of the glycated IgG was found to be significantly higher than the control IgG in the periods 524 h ( P <0.001, n = 6) and 24–48 h ( P <0.01, n =6) after injection. After 2–3 days the mice were killed and the major organs were harvested. With glycated IgG there was a significant increase in the 125 I accumulated in the kidney ( P <0.02). In later experiments, dual labelling with 131 I and 1251 allowed mixtures of glycated and unglycated IgG to be injected into the same mouse so that the vascular clearance of both forms of IgG could be followed simultaneously. These experiments confirmed that glycation of the IgG significantly increases its vascular clearance rate.