Hepatobiliary transport of plasma IgA in the mouse: contribution to clearance of intravascular IgA

Abstract

Labeled monomeric and polymeric (pIgA) mouse monoclonal IgA were injected intravenously into mice which were either sequentially bled for plasma turnover studies of IgA, or cannulated at their common bile duct, with excluded gallbladder, for quantitation of plasma-to-bile transport of pIgA. Our data show that mice do display a relatively high rate of biliary transport of plasma pIgA (22-28% of the injected 125I-labeled pIgA over 3 h), which accounts for approximately 90% of the total amount of pIgA (8.8 mg/kg/day) daily delivered by hepatic bile into the duodenal fluid of this species. However, in mice the absolute biliary output of pIgA does not exceed that of IgG (9.5 mg/kg/day) and the kinetics of the hepatobiliary transport of plasma pIgA appear to be slower than in the rat. Furthermore, as plasma survival studies of 125I-labeled pIgA yielded a plasma turnover of pIgA averaging 20.6 mg/kg/day, it can be approximated that the hepatobiliary pathway contributes for only 38% to the elimination of intravascular pIgA from mouse plasma, a figure to be compared to 89.8% in the rat and approximately 8.9% in man. We conclude that internal catabolism plays a dominant role in the clearance of intravascular pIgA in the mouse which appears as a model intermediate between rats and humans. Supporting this conclusion, serum pIgA two days after common bile duct ligation in 6 mice was increased by 2.5-fold vs. greater than 14-fold in ligated rats and 1.1-fold in humans with complete biliary obstruction.