Degradative intracellular transport of antisecretory component in cultured hepatocytes. An alternate pathway for the immunoglobulin A receptor.
The liver efficiently transports dimeric immunoglobulin A (dIgA) from blood to bile in a direct, nonlysosomal pathway involving smooth-surfaced vesicles. Secretory component (SC), the plasma membrane receptor for dIgA, is released into bile still bound to its ligand by disulfide bridges. Rabbit IgG antirat SC binds specifically to plasma membrane SC, yet the biliary secretion of anti-SC is markedly lower than that of dIgA, suggesting that the IgG antibodies utilize an alternate transhepatocellular pathway. Uptake of commercially available antihuman SC conjugated to horseradish peroxidase was examined by quantitative electron microscopic immunocytochemistry using primary rat hepatocyte monolayer cultures. Coincubation with human polymeric IgA, rabbit antiserum to rat SC, free human SC, human secretory IgA, and rat bile, all significantly suppressed uptake of anti-SC-horseradish peroxidase, thus demonstrating the specificity of the labeled antibody. Coated vesicles accounted for greater than 70% of the total uptake of either the anti-SC-horseradish peroxidase preparation or colloidal gold-labeled IgG antirat SC. Both compounds could also be observed in other structures associated with the degradative pathway, i.e., multivesicular bodies and lysosomes. Moreover, the extent to which 125I-anti-SC was degraded was significantly greater than that of 125I-dIgA. These data demonstrate that dIgA and anti-SC utilize different intracellular pathways, with anti-SC undergoing lysosomal degradation.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000032:analysis*; D001666:Binding Sites, Antibody; D001692:Biological Transport; D001826:Body Fluids / Q000378:metabolism*; D002478:Cells, Cultured; D007070:Immunoglobulin A / Q000378:metabolism; D007071:Immunoglobulin A, Secretory / Q000378:metabolism; D007128:Immunoglobulin Fragments / Q000276:immunology*; D007424:Intracellular Fluid / Q000378:metabolism*; D007457:Iodine Radioisotopes; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008954:Models, Biological; D051381:Rats; D011919:Rats, Inbred Strains; D011961:Receptors, Fc; D011971:Receptors, Immunologic / Q000378:metabolism*; D012635:Secretory Component / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; C045281:IgA receptor; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D007128:Immunoglobulin Fragments; D007457:Iodine Radioisotopes; D011961:Receptors, Fc; D011971:Receptors, Immunologic; D012635:Secretory Component