Polymeric IgA and Galactose-Specific Pathways in Rat Hepatocytes: Evidence for Intracellular Ligand Sorting

Abstract

In 1974 three papers appeared that triggered the investigations reported in this chapter. Ashwell and Morell (1974), respectively at the NIH and at Albert Einstein, New York, described the specific uptake by hepatocytes of galactose-exposing proteins and their rapid degradation in lysosomes. The same year, Brandtzaeg (1974), at the Institute of Pathology of the Rikshospitalet, Oslo, Norway, proposed a model for the selective transfer of polymeric IgA (pIgA) across mucous and glandular epithelia. Brandtzaeg’s proposal implied the selective binding of pIgA to a receptor called secretory component (SC), exposed at the basolateral surface of epithelial cells. SC would mediate pIgA translocation to the apical surface and into secretion, and protect pIgA from lysosomal degradation. This model, “based on test tube experiments with purified proteins and on immunofluorescence studies on dead tissues” (Brandtzaeg, 1981), was essentially correct but called for further work on living epithelia. Yet the same year, Heremans’ laboratory at the University of Louvain in Belgium reported the selective secretion of IgA into dog bile (Dive et al., 1974). Later, pIgA was also shown to be rapidly and actively secreted from blood to bile by rat liver (Jackson et al., 1978; Lemaitre-Coelho et al., 1978; Orlans et al., 1978) and the role of SC as pIgA receptor on rat hepatocytes was demonstrated (Fisher et al., 1979; Orlans et al., 1979; Socken et al., 1979).