IgA-mediated clearance and tissue deposition of dinitrophenylated human serum albumin at various DNP:HSA ratios.
Dinitrophenylated human serum albumin (DNP-HSA) with various DNP:HSA ratios was prepared by direct conjugation with dinitrobenzene sulfate or with a caproic acid spacer group (DNP-cap-HSA) using DNP-epsilon-amino-caproic acid N-hydroxy-succinimide ester. The substitution ratio and chemical linkage (presence of a spacer group) were shown to affect the degree of murine anti-DNP antibody binding to antigen, and hence the tissue deposition and efficiency of hepatobiliary transport. DNP-HSA (4.5:1), which poorly binds to IgA anti-DNP antibody, is inefficiently transported into mouse bile. In contrast, 9:1 DNP-cap-HSA readily forms complexes and is more effectively cleared by the hepatobiliary route. The IgA-mediated increase in liver deposition of DNP-cap-HSA (9:1) was found to be associated with an increase in antigen uptake by hepatocytes. In contrast, large complexes formed between DNP-HSA (49:1) and IgA anti-DNP antibody are taken up by nonparenchymal cells of the liver and thus are inefficiently transported into bile. These results suggest that the IgA-mediated uptake by phagocytic cells or hepatocytes of haptenated protein strongly depends on the degree of haptenation.
Epps
J M
JM
Department of Microbiology and Medicine, University of Alabama, Birmingham 35294.
Phillips
J O
JO
Mestecky
J
J
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism; D001646:Bile / Q000276:immunology; D004140:Dinitrophenols / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D008099:Liver / Q000276:immunology; D051379:Mice; D012709:Serum Albumin / Q000378:metabolism*; D013154:Spleen / Q000276:immunology
D000936:Antigen-Antibody Complex; D004140:Dinitrophenols; D007070:Immunoglobulin A; D012709:Serum Albumin; C058064:dinitrophenyl-human serum albumin conjugate