The sites of catabolism of murine monomeric IgA.
The tissue sites of monomeric IgA (mIgA) catabolism were determined in a BALB/c mouse model. Mouse mIgA myeloma proteins were labeled either by direct iodination or by coupling the residualizing label, dilactitol-125I-tyramine (125I-DLT) to the proteins; catabolites from protein labeled with 125I-DLT accumulate at the site of protein degradation, allowing identification of the tissue and cellular sites involved in catabolism of the protein. The circulating half-lives of 125I- and 125I-DLT-mIgA were the same. The distribution of radioactivity in tissues was measured at 1, 3, 24, and 96 h after iv. injection of 125I-DLT-labeled mIgA, dimeric IgA (dIgA), IgG, or mouse serum albumin. The greatest uptake of 125I-DLT-mIgA was attributable to the liver. This organ accounted for more internal catabolism of mIgA than all other tissues combined. In contrast, 125I-DLT-IgG was catabolized equally in skin, muscle, and liver. These data indicate that, in mice, the liver is the major site of mIgA catabolism. To determine the cell types involved, collagenase digestion was used to isolate parenchymal and non-parenchymal cells from perfused liver of animals injected with 125-DLT-mIgA. Most of the radioactivity was associated with the hepatocyte fraction, even though both cell types showed uptake of 125I-DLT-mIgA. Inhibition studies, with asialofetuin and mouse IgA demonstrated that the uptake of mIgA by liver cells was mediated primarily by the asialoglycoprotein receptor.
Moldoveanu
Z
Z
Department of Microbiology, University of Alabama, Birmingham 35294.
Epps
J M
JM
Thorpe
S R
SR
Mestecky
J
J
D000818:Animals; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D005260:Female; D060748:Fetuins; D007070:Immunoglobulin A / Q000378:metabolism*; D007457:Iodine Radioisotopes / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009132:Muscles / Q000378:metabolism; D011961:Receptors, Fc; D011971:Receptors, Immunologic / Q000032:analysis; D012867:Skin / Q000378:metabolism; D014439:Tyramine / Q000031:analogs & derivatives / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000378:metabolism
D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D060748:Fetuins; C045281:IgA receptor; D007070:Immunoglobulin A; D007457:Iodine Radioisotopes; D011961:Receptors, Fc; D011971:Receptors, Immunologic; D000509:alpha-Fetoproteins; C017029:asialofetuin; C049133:dilactitol tyramine; D014439:Tyramine