Changes in IgA Following Varying Degrees of Biliary Obstruction in the Rat

Abstract

Polymeric IgA is rapidly transported from blood to bile by the rat liver. The effect of varying degrees of biliary obstruction on this transport process was studied. IgA concentrations were measured by radioimmunoassay. Serum IgA concentrations increased progressively, and IgA output in bile declined with increasing bile duct obstruction. The decline in bile IgA output was explained by both diminished bile flow and decreased concentrations of IgA in bile. Very little polymeric IgA was present in normal rat serum. In contrast, using column chromatography on Ultrogel AcA 22, increases in serum IgA associated with cholestasis were shown to be due to increments in polymeric IgA. Serum IgA was a more sensitive indicator of cholestasis than was serum alkaline phosphatase. IgA and secretory component were found, using indirect immunofluorescence, surrounding bile canaliculi and on or adjacent to the hepatocyte plasma membrane lining the sinusoids. With biliary obstruction, staining for IgA and secretory component intensified markedly near the bile canaliculi. We conclude that: (a) polymeric IgA must be efficiently removed from serum by the normal rat liver; (b) even minimal cholestasis impairs IgA output into bile, and (c) impairment of IgA transport during cholestasis appears to occur at or near the canalicular membrane.