Hepatic uptake and disposition of human polymeric IgA1 in perfused rat liver: evidence for incomplete biliary excretion and intrahepatic degradation.
The hepatic uptake of polymeric immunoglobulin A (IgA) is mediated by secretory component; the resulting secretory IgA is excreted intact into bile. To define the hepatic metabolism of polymeric IgA, we quantitated the uptake and transport of human polymeric IgA1 after a single pass through the perfused rat liver. Uptake of polymeric IgA1 was compared with that of asialoorosomucoid, a glycoprotein whose uptake is mediated by the asialoglycoprotein receptor. Single-pass hepatic uptake of 125I-polymeric IgA1 and of 125I-asialoorosomucoid averaged 18.0 +/- 3.1% (SE) and 71.8 +/- 2.8%, respectively. The uptake of 125I-polymeric IgA1 was inhibited by excess unlabeled polymeric IgA1 but not by asialoorosomucoid. Only 13.0 +/- 1.6% of the 125I-polymeric IgA1 extracted by the liver was excreted into bile, whereas three-fourths was released into the hepatic venous effluent in degraded form. Thus, both the uptake and biliary excretion of polymeric IgA1 by the rat liver are inefficient processes. Polymeric IgA1 follows two distinct pathways after uptake by the liver: a small proportion is excreted intact into bile, while the majority is degraded and released back into the circulation.
D000818:Animals; D001212:Asialoglycoproteins; D001646:Bile / Q000378:metabolism*; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D007071:Immunoglobulin A, Secretory / Q000378:metabolism; D007128:Immunoglobulin Fragments / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D009961:Orosomucoid / Q000031:analogs & derivatives / Q000378:metabolism; D010477:Perfusion; D011108:Polymers; D051381:Rats; D011919:Rats, Inbred Strains; D011971:Receptors, Immunologic / Q000378:metabolism; D012635:Secretory Component / Q000378:metabolism*; D013997:Time Factors
D001212:Asialoglycoproteins; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D007128:Immunoglobulin Fragments; D007457:Iodine Radioisotopes; D009961:Orosomucoid; D011108:Polymers; D011971:Receptors, Immunologic; D012635:Secretory Component; C017030:asialoorosomucoid; C034639:polymeric IgA