Postsynthetic modification of human. cap alpha. -fetoprotein controls its immunosuppressive potency

Journal Article · Thu Sep 01 00:00:00 EDT 1977 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.74.9.3988· OSTI ID:7277186

Lester, E P; Miller, J B; Yachnin, S

In a previous study three variants of human ..cap alpha..-fetoprotein were demonstrated by crossed immunoelectrophoresis. In addition, the capacity of ..cap alpha..-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 was correlated. We have now isolated ..cap alpha..-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 ..cap alpha..-fetoprotein were found to be extremely potent, serum ..cap alpha..-fetoprotein had intermediate potency, and ascitic fluid ..cap alpha..-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 ..cap alpha..-fetoprotein isolates did not vary significantly. Our data suggest that a postsynthetic modification of ..cap alpha..-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.

• Research Organization: Univ. of Chicago
• OSTI ID: 7277186
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 74:9; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
550500 -- Metabolism
550600 -- Medicine
59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMAL CELLS
ANIMALS
ASCITES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD PLASMA
BODY
BODY FLUIDS
CARBOHYDRATES
CONNECTIVE TISSUE CELLS
DIGESTIVE SYSTEM
DISEASES
ELECTROPHORESIS
FETUSES
GLANDS
GLOBULINS
GLUCOPROTEINS
HEPATOMAS
IMMUNE REACTIONS
IMMUNOGLOBULINS
IMMUNOSUPPRESSION
LEUKOCYTES
LIVER
LYMPHOCYTES
MAMMALS
MAN
NEOPLASMS
ONTOGENESIS
ORGANIC COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
POLYSACCHARIDES
PRIMATES
PROTEINS
SACCHARIDES
SIALIC ACID
SOMATIC CELLS
SYMPTOMS
VERTEBRATES