Identification of the First Receptor for a Pregnancy Specific Glycoprotein. Tetraspanins Find Their Ligand
Uniformed Services University Of The Health Sciences Bethesda United States
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Pregnancy specific glycoproteins PSGs are a family of secreted proteins produced by the placenta, which have been shown to be essential for pregnancy success. The ability of human PSGs to induce anti-inflammatory cytokines has led to the hypothesis that these proteins may function to protect the fetus from attack by the maternal immune system. With the purpose of developing an animal model to study the function of PSGs, we have studied the effects of murine PSG17 on macrophages and we have cloned its receptor. RAW 264.7 cells and peritoneal macrophages were treated with recombinant PSG17N, which consists of the N-domain of PSG17. PSG17N induced production of IL-10 and IL-6 at the protein and RNA levels in these cells. Secretion of TGFbeta1 and PGE2 was also induced upon treatment with PSG17N. We then examined the PSG17-RAW cell surface binding interaction. Scatchard analysis revealed that there are approximately 1770 binding sites per cell with a Kd of 2.2 X 10exp-11 M. For the purpose of cloning the PSG17 receptor, we screened a RAW cell eDNA library by panning. The receptor was identified as CD9, a member of the tetraspanin superfamily.
- Medicine and Medical Research