The role of the liver in catabolism of mouse and human IgA.
The fate of intravascular IgA which is produced in large quantities in humans and many animal species was investigated in vivo and in vitro with emphasis on the monomeric form of IgA. The site(s) of the catabolism of intravenously injected mouse monomeric IgA labeled with a residualizing tracer (dilactitol - 125I tyramine) was studied in mice. The greatest in vivo uptake of monomeric IgA was observed in the liver. In contrast to identically labeled IgG, liver accounted for more internal catabolism of monomeric IgA than all other tissues (spleen, muscle, skin, and kidney) combined. Although both parenchymal and nonparenchymal liver cells internalized monomeric IgA, hepatocytes were far more active. The uptake of monomeric IgA was primarily mediated by the asialoglycoprotein receptor. In humans, the particulate fraction of liver homogenates and a human hepatoma cell line (Hep G2) bound human IgA proteins of various molecular forms. Inhibition of the binding by desialylated glycoproteins, requirement for the presence of calcium, and the molecular properties of the IgA-binding protein from the plasma membrane of Hep G2 cells indicated that the binding was primarily mediated by the asialoglycoprotein receptor. IgA proteins bound by Hep/G2 cells were internalized and catabolized to low molecular weight fragments.
Mestecky
J
J
Department of Microbiology, University of Alabama, Birmingham 35294.
Moldoveanu
Z
Z
Tomana
M
M
Epps
J M
JM
Thorpe
S R
SR
Phillips
J O
JO
Kulhavy
R
R
D000818:Animals; D037263:Asialoglycoprotein Receptor; D001693:Biological Transport, Active; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D008099:Liver / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D011971:Receptors, Immunologic / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000276:immunology
D037263:Asialoglycoprotein Receptor; D007070:Immunoglobulin A; D011971:Receptors, Immunologic