Glycation increases thevascular clearance rateofIgGinmice

SUMMARY Aselevated levels ofglycated IgGhavebeendetected intheplasma ofdiabetics we haveinvestigated whether glycation ofIgGaffects its vascular clearance rate, using a mouse modelsystem. Polyclonal mouse IgGwas aseptically incubated for14-19dayswith05M glucose in0-1 M phosphate buffer (pH 7-4) at37°C. Ascontrol, IgGwas incubated underidentical conditions butwithno addedglucose. After incubation, bothforms werelabelled with125I andinjected intravenously intoBALB/cmice. Therateofvascular clearance oftheglycated IgGwas foundtobesignificantly higher thanthe control IgGintheperiods 5-24h(P< 0-001, n = 6)and24-48h(P< 0-01, n = 6)after injection. After 2-3daysthemicewere killed andthemajor organswere harvested. Withglycated IgGthere was a significant increase inthe1251 accumulated inthekidney (P< 0-02). Inlater experiments, dual labelling with'3'I and1251 allowed mixtures ofglycated andunglycated IgGtobeinjected intothe same mouse sothatthevascular clearance ofbothformsofIgGcouldbefollowed simultaneously. Theseexperiments confirmed thatglycation oftheIgGsignificantly increases itsvascular clearance rate.