Endocytosis of three serum proteins of a multigene family and of arachidonic acid in human lectin‐stimulated T lymphocytes

Abstract

Alpha-fetoprotein (AFP), serum albumin (SA), and vitamin D binding protein (DBP) are members of a multigene family of proteins showing high structural homology. AFP and SA exhibit a reciprocal relation during development and carry mostly fatty acids, while DBP carries vitamin D and its metabolites in the plasma. Covalent conjugates of these proteins with horseradish peroxidase (HRP) were used to follow by cytochemistry, at the electron microscope level, the protein uptake and intracellular pathways in peripheral blood human lymphocytes stimulated to blast formation by phytohemagglutinin (PHA). Transferrin (Tf), an iron-binding plasma protein, was used as a control. Combined with the results of competition and saturability experiments reported elsewhere, the ultrastructural observations are in favour of a specific endocytosis of the four proteins through cell surface receptors. Tf and AFP enter the cells via small vesicles and endosomes and move to multivesicular bodies (MVBs) and tubular vesicular elements located in the Golgi-centrosphere region to be finally recycled back into the medium. A noncovalent conjugate of AFP-HRP with 3H arachidonic acid [3H-(20:4)] is strongly internalized at 37 degrees C in PHA-stimulated lymphocytes; the autoradiographic labelling, localized in cellular membranes and mostly in lipid droplets, was only occasionally associated with organelles where the presence of AFP-HRP was cytochemically detected. SA, which competes with AFP for a common binding site on the surface of activated T cells, is endocytosed through small vesicles, endosomes, and MVBs before being released in a degraded form from the cells, in agreement with the localization of SA-HRP in lysosome-like organelles. DBP-HRP is poorly internalized through noncoated vesicles, endosomes, and MVBs and is finally routed to lysosomes. The physiological role of AFP and SA would be to mediate the transfer of fatty acids into cells, while that of DBP would be to facilitate the intracellular delivery of vitamin D.

Gc-globulin is an acute phase reactant and an indicator of muscle injury after spinal surgery

“…Another interaction between lymphocytes and Gc-globulin has been described. Both human B-lymphoid cells, and activated normal B-and T-lymphocytes take up Gc-globulin [35,36]. It has been suggested that the physiological role of this endocytosis could be facilitation of intracellular delivery of vitamin D, supporting the hypothesis that delivery of vitamin D metabolites plays a role in the physiologic response to injury [21].…”

True

“…Habenicht et al (1990) have demonstrated that cholesteryl-AA is taken up by the cells via the LDL receptor pathway. Serum albumin-bound AA enters the cells by endocytosis (Geuskens et al, 1994;Iturralde et al, 1991;Uriel et al, 1994). After transportation into the cells, AA is incorporated into the lipid pool as part of phospholipids (Chilton et al, 1996).…”

Induction of Apoptosis in Human Hepatoma Cells by Alpha-Fetoprotein

“…Arachidonic acid and some other polyunsaturated fatty acid metabolites, derived from the lipoxygenase pathway, have also been shown to be selectively toxic for transformed cells [42,43]. Taking into ac count data showing that AFP can mediate the uptake of fatty acids by AFPr+ cells [44,45], the cytotoxic AFP activity could be attributed to its biologically active ligands. We show here that charcoal-treated ligand-free eAFPp revealed a strong dose-dependent growth-in hibitory activity similar to intact eAFP, but slightly less intensive.…”