Carbohydrate-mediated clearance of secretory IgA from the circulation.
Radioiodinated human secretory IgA (sIgA) injected intravenously into mice was rapidly cleared from the circulation by the liver. A portion of the sIgA was transported as an intact molecule into the bile. However, this transport was less efficient than that of human serum polymeric IgA (pIgA). The clearance of sIgA from the circulation was inhibited by prior injection of asialofetuin, suggesting that its uptake is mediated by the hepatic binding protein (HBP) specific for asialoglycoproteins. Mouse pIgA did not inhibit the hepatic clearance of sIgA. Results of in vivo studies were confirmed by in vitro experiments. The binding of 125I-asialoorosomucoid to either the particulate fraction (2000 g pellet of the homogenate) or the plasma membrane fraction of mouse liver was inhibited by sIgA. When polypeptide components of sIgA were used as inhibitors, significant inhibition was obtained with secretory component (SC), while inhibition with light and J-chains was not statistically significant. Examination of the inhibitory activity of IgA1 and IgA2 myeloma proteins and heavy chains isolated from these proteins revealed that binding of polymeric IgA1 and alpha 1 heavy chains can also be mediated by HBP. However, these interactions appear to be of lower avidity than those with SC. The inhibitory activity of human IgA2 and alpha 2 heavy chains was not significant. The involvement of HBP in binding of sIgA was also confirmed by measuring the inhibition of binding of 125I-sIgA. The binding of this protein by the particulate fraction of the mouse liver homogenate was inhibited by asialoglycoproteins and SC while inhibition with IgA1 and alpha 1 heavy chains was not significant. These results suggest that the carbohydrate moieties recognized by HBP reside primarily in the SC portion of sIgA.
Tomana
M
M
Phillips
J O
JO
Kulhavy
R
R
Mestecky
J
J
D000818:Animals; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D002241:Carbohydrates / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D060748:Fetuins; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D007071:Immunoglobulin A, Secretory / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007700:Kinetics; D008099:Liver / Q000276:immunology / Q000378:metabolism*; D008110:Liver Extracts / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009961:Orosomucoid / Q000031:analogs & derivatives / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000494:pharmacology
D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D002241:Carbohydrates; D002352:Carrier Proteins; D060748:Fetuins; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D007457:Iodine Radioisotopes; D008110:Liver Extracts; D009961:Orosomucoid; D000509:alpha-Fetoproteins; C017029:asialofetuin; C017030:asialoorosomucoid; C027122:hepatic sialoglycoprotein receptor; C034639:polymeric IgA