Hepatic asialoglycoprotein receptor-mediated binding of human polymeric immunoglobulin A.
In the rat, asialoorosomucoid and rat dimeric immunoglobulin A are both taken up by hepatocytes via receptor-mediated endocytosis. The fate of these two proteins, however, differs significantly. Rat dimeric IgA is taken up into smooth vesicles, transported to the bile canaliculus and secreted intact into the bile, whereas asialoglycoproteins are internalized via coated vesicles and transported to lysosomes for degradation. Recently, several studies both in the rat and in cultured human hepatoma cells have suggested that the receptor for asialoglycoproteins may play a role in the hepatic uptake and processing of human polymeric IgA. Using receptor-binding techniques, we have provided quantitative data for the competition of human monomeric, polymeric and secretory IgA with asialoorosomucoid for its receptor on liver plasma membrane preparations from rat, monkey and man. Some IgA molecules required desialylation with neuraminidase to enhance markedly their efficacy for asialoorosomucoid inhibition. Quantitatively, human IgA molecules showed an affinity for the ASOR receptor similar to that for asialoceruloplasmin. Rat dimeric IgA does not compete for this binding site. We conclude that human IgA can compete with ligands for the asialoglycoprotein receptor of rat, monkey and human liver. This receptor may provide an alternative pathway for the hepatic processing of IgA and IgA immune complexes when secretory component-mediated uptake is not available as in the monkey and man, particularly under pathological conditions where serum IgA concentrations accumulate to abnormally high levels.
Daniels
C K
CK
Cell Biology and Aging Section, Veterans Administration Medical Center, San Francisco, California 94121.
Schmucker
D L
DL
Jones
A L
AL
D000818:Animals; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D007071:Immunoglobulin A, Secretory / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008253:Macaca mulatta; D046911:Macromolecular Substances; D008297:Male; D009101:Multiple Myeloma / Q000276:immunology; D009439:Neuraminidase / Q000494:pharmacology; D009961:Orosomucoid / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011971:Receptors, Immunologic / Q000378:metabolism*
D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D046911:Macromolecular Substances; D009961:Orosomucoid; D011971:Receptors, Immunologic; C017030:asialoorosomucoid; C034639:polymeric IgA; D009439:Neuraminidase