Intracellular processing of human vs. rat immunoglobulin A in the rat liver.
It is well established that in the rat, rat dimeric IgA is transported from blood to bile across rat liver parenchymal cells via a series of minute smooth membrane-limited vesicles. This pathway is unique from that taken by a number of other ligands, which are internalized for degradation, in that there appears to be little involvement of coated vesicles, multivesicular bodies and lysosomes. The transmembrane receptor for IgA, secretory component, is not recycled but is secreted in part with the ligand into bile and must be produced continuously within the liver cell. Several recent studies have suggested that the receptor for asialoglycoproteins, as well as the structures involved in its processing, may play an important role in IgA processing. It was noted, however, that in all of these studies human polymeric IgA1 was used in the rat model. Using purified rat and human IgA preparations, we have demonstrated by light and quantitative electron microscopic autoradiography, as well as by certain biochemical procedures, that the two ligands are processed quite differently from one another in the rat. Human IgA disappears from the plasma at a slower rate and is much less efficiently transported into the bile. In addition, up to as much as 30% of the human IgA is diverted to the lysosomal pathway. This diversion of human polymeric IgA may be related to either the association of a serine-linked oligosaccharide at the hinge region of the human polymeric IgA1 or that large polymers, often found in human IgA preparations may initiate secretory component receptor aggregation, which in turn, interferes with the normal physiological processing of the IgA molecule.
D000818:Animals; D001345:Autoradiography; D001646:Bile / Q000378:metabolism; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D011916:Rats, Inbred F344; D012635:Secretory Component / Q000096:biosynthesis
D007070:Immunoglobulin A; D012635:Secretory Component; C034639:polymeric IgA