Saturation of the Reticuloendothelial System with Soluble Immune Complexes

Abstract

The clearance kinetics of passively administered soluble human serum albumin (HSA)antiHSA complexes were studied in mice at varied doses. Complexes with a molecular composition exceeding Ag₂Ab₂ (τ 11S complexes) were preferentially cleared by the hepatic reticuloendothelial system. As the dose of administered complexes was increased to levels known to induce glomerulonephritis, however, saturation of the reticuloendothelial system occurred. Three lines of evidence supported this conclusion: 1) The proportion of injected complexes cleared with the fastest half-life became less as the dose was increased. 2) Saturation was demonstrated in the first-order reaction that describes the clearance of τ 11 S complexes (τ Ag₂Ab₂). 3) The specific hepatic uptake of complexes approached a maximum as the dose was increased. Due to saturation of the reticuloendothelial system, the τ 11 S complexes persisted in the circulation and thereby the likelihood of their non-hepatic tissue deposition was enhanced. The possible contribution of saturation of the reticuloendothelial system to the pathogenesis of glomerulonephritis in experimental serum sickness is discussed.