Uptake of 125I-labelled α2-macroglobulin and albumin by human placental syncytiotrophoblast in vitro
✍ Scribed by Gordon C. Douglas; Patricia Moreira-Cali; Barry F. King; Bo Lonnerdal
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 113 KB
- Volume
- 68
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
We have investigated the binding and internalization of ␣ 2 -macroglobulin and serum albumin by human placental syncytiotrophoblast cells in vitro. The time course (obtained at 4°C) of ␣ 2 -macroglobulin binding indicated that an equilibrium was reached after 4 h. The binding of 125 I-labelled ␣ 2 -macroglobulin to syncytiotrophoblast cells was competitively reduced in the presence of excess unlabelled ␣ 2 -macroglobulin. When the concentrationdependence of binding was examined over a wide concentration range, non-linear regression analysis yielded a K d of 6.4 nM. In the case of albumin, binding was weak and ligand dissociated from the cell surface during aqueous washing making it impractical to analyze the binding reaction. In other experiments, syncytiotrophoblast cells were incubated with 125 I-labelled ␣ 2 -macroglobulin at 37°C. Under these conditions, trypsin-resistant cell-associated radioactivity increased with time consistent with ligand internalization. 125 I-Labelled-ligand was internalized with a t 1/2 of about 5 min. After a lag period some radioactivity was released back into the incubation medium. When measured at times up to 210 min, this was found to consist of mostly TCA-precipitable material that had been lost from the cell surface. However, when the incubation was extended to 24 h, almost 15% of the initial cell-associated radioactivity was released to the extracellular medium as TCA-soluble material, consistent with a slow rate of ligand degradation. The specific binding of 65 Zn-labelled ␣ 2 M was similar to that of the 125 I-labelled ligand and trypsin-resistance measurements provided evidence of ␣ 2 M-mediated 65 Zn uptake. These results support a role for syncytiotrophoblast in the metabolism of ␣ 2macroglobulin during pregnancy and are also consistent with a role for ␣ 2 -macroglobulin in the maternal-fetal transport of zinc.