Lipid interactions with human alpha-fetoprotein (AFP). A study of the role of such interactions in the ability of human AFP to suppress lymphocyte transformation.
The ability of human alpha-fetoprotein (HAFP) isolates to inhibit human lymphocyte transformation varies over 2-3 orders of magnitude. Since HAFP is known to bind fatty acids, we have examined the possible role of lipid binding in producing this variability. While certain oxygenated sterols are potent inhibitors of lymphocyte transformation, and while the kinetics of such inhibition precisely mimic those of HAFP, HAFP is, by contrast, a weak inhibitor of sterol synthesis in mitogen-stimulated human lymphocytes. Fatty acids (18:0, 18:1, 18:2, 18:3, 20:4, 22:6) and 10(-4) M have little or no effect upon lymphocyte transformation. The fatty acid content of seen HAFP isolates ranged from 2.3 to 8.0 mol fatty acid/mol HAFP and included 12:0, 14:0, 16:0 (the most abundant), 18:0, 20:4, and 22:0; no 22:6 was found. There was no correlation between the total or individual fatty acid contents of HAFPs and their ability to inhibit lymphocyte transformation. Lysooleoyl-, lysostearoyl-, and lysopalmitoyl-lecithin at 5 X 10(-5) M all inhibited lymphocyte transformation (30.1%, 52.1%, and 58.1%, respectively) and the latter was active at 6.3 X 10(-6) M. Exposure of HAFP to a 5-fold molar excess of [14C]-lysopalmitoyl lecithin resulted in significant (10%) binding to HAFP, while no significant binding of dipalmitoyl lecithin occurred under similar conditions. Analysis of lipid extracts of potent HAFP isolates by thin-layer chromatography failed to reveal the presence of phospholipids. Although HAFP can bind certain lipids, and although certain lipids inhibit lymphocyte transformation, we conclude that HAFP suppression of lymphocyte transformation cannot be attributed to the binding of hydrocortisone, prostaglandins, fatty acids, lysolecithins, or oxygenated sterol compounds.
D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000096:biosynthesis; D005227:Fatty Acids / Q000097:blood; D006801:Humans; D007700:Kinetics; D008055:Lipids / Q000097:blood*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000378:metabolism; D010743:Phospholipids / Q000097:blood; D013261:Sterols / Q000097:blood; D000509:alpha-Fetoproteins / Q000378:metabolism* / Q000494:pharmacology
D005227:Fatty Acids; D008055:Lipids; D010743:Phospholipids; D013261:Sterols; D000509:alpha-Fetoproteins; D004247:DNA