Isolation and partial characterization of a specific alpha-fetoprotein receptor on human monocytes.

Abstract

Since a large body of data has suggested a significant role for alpha-fetoprotein (AFP) in the regulation of the immune response at a number of levels, we examined the possibility of a specific receptor for AFP on the immune recognition cell, the monocyte/macrophage. Microscopic autoradiography exhibited an obvious binding of AFP almost exclusively on human peripheral monocytes but not on lymphocytes. In a human monocyte cell line (U937) Scatchard plot analysis indicated the presence of two distinct AFP-specific binding sites with a Kd of 5 X 10-11 M, 49 binding sites per cell, and 2.5 X 10-7 M, 7,800 binding sites per cell. 125I-ASD-AFP, AFP-radiolabeled bifunctional photoactivatable thio-cleavable cross-linker, was used to isolate the AFP binding protein from U937 cells. After ultraviolet photoactivation, 125I-sulfosuccinimidyl 2-(p-azidosalicylamido)ethyl-1,3'-dithiopropionate was covalently linked to the putative receptor. Autoradiography of SDS gradient PAGE under reducing conditions showed a major radiolabeled band at between 62 and 65 kD. To confirm the specificity of the finding, recombination of AFP with the isolated receptor was examined in artificially reconstituted membrane vesicles, which also resulted in a single band at 62-65 kD by SDS-PAGE autoradiography. From the data above, we concluded that human monocytes possess a specific AFP binding protein on the membrane, a putative receptor, which may be involved with the physiological regulation of the immune response. (J.

Alpha-fetoprotein, the major fetal serum protein, is not essential for embryonic development but is required for female fertility

“…Receptor-mediated endocytosis could allow cell type-specific delivery of AFP, in a similar manner to the renal uptake of the complex formed by the vitamin D binding protein (which is related to AFP) and vitamin D3 (40). AFP receptors have been described (41,42) and specific uptake of AFP by some cells, especially developing neurons, has been reported (43,44). This uptake probably explains the presence of AFP in neurons (45,46), because AFP is not synthesized in the brain (ref.…”

Differences between human and mouse alpha‐fetoprotein expression during early development

“…However, AFP can be taken up by a variety of cell types so its actions may not be limited to the cells actually synthesising AFP. It is known that there are specific cellular receptors for the uptake of AFP (Mizejewski, 1995 ;Susuki et al 1992). It has been shown that AFP liganded to a fatty acid is endocytosed via clathrin-coated receptosomes, transported to the endoplasmic reticulum and Golgi complex and released into the cell in an intact form rather than being degraded in a lysosome (Antohe et al 1993).…”

The intracellular mechanism of alpha-fetoprotein promoting the proliferation of NIH 3T3 cells

“…However, little information regarding the biochemical features of alpha-fetoprotein determined using molecular biological techniques is available. Although it is currently thought that a 62-to 67-kDa membrane protein on the surface of monocytes and phagocytes is specific for AFP [6][7], the properties of the binding sites were still unknown in most tumor cell lines. Furthermore, few studies have focused on its intracellular signaling events and gene expression.…”