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Media type:
E-Article
Title:
A Postsynthetic Modification of Human α -fetoprotein Controls Its Immunosuppressive Potency
Contributor:
Lester, Eric P.;
Miller, J. Bruce;
Yachnin, Stanley
imprint:
National Academy of Sciences of the United States of America, 1977
Published in:Proceedings of the National Academy of Sciences of the United States of America
Language:
English
ISSN:
0027-8424
Origination:
Footnote:
Description:
<p>In a previous study, we demonstrated three variants of human α -fetoprotein by crossed immunoelectrophoresis. In addition, we correlated the capacity of α -fetoprotein isolates from various hepatoma and fetal sources to suppress human lymphocyte transformation in vitro with the relative proportion of the electronegative variant, HAFP-3, present in each isolate. We have now isolated α -fetoprotein from the serum, ascitic fluid, and saline extract of tumor from a single hepatoma patient and from a homogenate of fetal livers. When tested for their capacity to inhibit human lymphocyte transformation in vitro, tumor and fetal liver α -fetoprotein were found to be extremely potent, serum α -fetoprotein had intermediate potency, and ascitic fluid α -fetoprotein was the least potent. Analysis of these isolates by crossed immunoelectrophoresis confirmed the correlation between the proportion of HAFP-3 and the immunosuppressive potency of each isolate. In addition, analysis of these isolates by isoelectric focusing in polyacrylamide gels containing 8 M urea revealed further evidence of microheterogeneity; at least six molecular variants were apparent. The proportion of one of these variants, termed HAFP-3a, in each isolate was correlated with the immunosuppressive potency of the isolate. The sialic acid content of the various α -fetoprotein isolates did not vary significantly. Our data suggest that a postsynthetic modification of α -fetoprotein occurs, probably after secretion, which reduces immunosuppressive potency by converting the active electronegative species to an inactive electropositive form. This modification probably involves a charged moiety other than sialic acid on the molecule.</p>