CLEARANCE PATHWAYS OF SOLUBLE IMMUNE-COMPLEXES IN THE PIG - INSIGHTS INTO THE ADAPTIVE NATURE OF ANTIGEN CLEARANCE IN HUMANS

Efficient delivery of immune complexes (ICs) to the mononuclear phagoc ytic system, and subsequent IC processing, may prevent their potential ly harmful effects in other tissues and may also be important in the d evelopment of humoral immune responses. In mice, rabbits, and primates , the liver acid spleen are the main sites of IC clearance. It has bee n demonstrated previously that the pulmonary capillaries in the pig ar e lined with macrophages and that certain particulates, including bact eria, localize to this organ. In this study, we used gamma scintigraph y to explore the sites and kinetics of clearance of soluble IC compris ing I-123-labeled hepatitis fl surface Ag (HBsAg):porcine anti-HBsAg i n the Large White pig. At t = 10 min after i.v. injection, 43 +/- 5% ( mean +/- SE) IC localized in the lungs, and 36 +/- 6% counts in the li ver. At t = 85 min, values were: lungs, 15 +/- 4% and liver, 29 +/- 2% . Findings were similar following intraarterial injection. Complement depletion resulted in more rapid initial IC clearance (t(1/2) = 5 min) , reduced lung uptake (23 +/- 3% at 10 min), and impaired IC catabolis m. In normal animals, 5 to 7% injected IC bound to PBMCs, but no E bin ding, was seen. A fall in PBMC numbers (46 to 59% of baseline), was ob served following IC injection. These findings contrast with our previo us observations using analogous IC in humans, in which we did not obse rve any change in peripheral blood leukocyte counts consequent upon co mplex processing, suggesting that in humans, Es may function as a buff ering system for complement-bearing IC in the circulation, preventing their interaction with leukocytes bearing complement and FcR, and the potential activation of these cells.