Peer Reviewed

1

Document Type

Article

Publication Date

2013

Keywords

Pregnancy-Specific Glycoproteins, Integrin αIIbβ3, Platelet-Fibrinogen Interaction

Abstract

Pregnancy-specific glycoproteins (PSGs) are immunoglobulin superfamily members encoded by multigene families in rodents and primates. In human pregnancy, PSGs are secreted by the syncytiotrophoblast, a fetal tissue, and reach a concentration of up to 400 ug/ml in the maternal bloodstream at term. Human and mouse PSGs induce release of anti-inflammatory cytokines such as IL-10 and TGFb1 from monocytes, macrophages, and other cell types, suggesting an immunoregulatory function. RGD tri-peptide motifs in the majority of human PSGs suggest that they may function like snake venom disintegrins, which bind integrins and inhibit interactions with ligands. We noted that human PSG1 has a KGD, rather than an RGD motif. The presence of a KGD in barbourin, a platelet integrin aIIbb3 antagonist found in snake venom, suggested that PSG1 may be a selective aIIbb3 ligand. Here we show that human PSG1 binds aIIbb3 and inhibits the platelet – fibrinogen interaction. Unexpectedly, however, the KGD is not critical as multiple PSG1 domains independently bind and inhibit aIIbb3 function. Human PSG9 and mouse Psg23 are also inhibitory suggesting conservation of this function across primate and rodent PSG families. Our results suggest that in species with haemochorial placentation, in which maternal blood is in direct contact with fetal trophoblast, the high expression level of PSGs reflects a requirement to antagonise abundant (3 mg/ml) fibrinogen in the maternal circulation, which may be necessary to prevent platelet aggregation and thrombosis in the prothrombotic maternal environment of pregnancy.

Disciplines

Life Sciences

Citation

Shanley DK, Kiely PA, Golla K, Allen S, Martin K, O'Riordan RT, Ball M, Aplin JD, Singer BB, Caplice N, Moran N, Moore M. Pregnancy-Specific Glycoproteins Bind Integrin αIIbβ3 and Inhibit the Platelet-Fibrinogen Interaction. PLoS One. 2013;8(2):e57491

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