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Pregnancy-specific glycoproteins bind integrin alpha IIb beta 3 and inhibit the platelet-fibrinogen interaction

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dc.contributor.author Shanley, Daniel K.
dc.contributor.author Kiely, Patrick A.
dc.contributor.author Golla, Kalyan
dc.contributor.author Allen, Seamus
dc.contributor.author Martin, Kenneth
dc.contributor.author O'Riordan, Ronan T.
dc.contributor.author Ball, Melanie
dc.contributor.author Aplin, John D.
dc.contributor.author Singer, Bernhard B.
dc.contributor.author Caplice, Noel
dc.contributor.author Moran, Niamh
dc.contributor.author Moore, Tom
dc.date.accessioned 2014-04-08T13:37:31Z
dc.date.available 2014-04-08T13:37:31Z
dc.date.issued 2013
dc.identifier.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, T (2013) 'Pregnancy-Specific Glycoproteins Bind Integrin alpha IIb beta 3 and Inhibit the Platelet-Fibrinogen Interaction'. Plos One, 8 . en_US
dc.identifier.uri http://hdl.handle.net/10344/3768
dc.description peer-reviewed en_US
dc.description.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 mu g/ml in the maternal bloodstream at term. Human and mouse PSGs induce release of anti-inflammatory cytokines such as IL-10 and TGF beta 1 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 alpha IIb beta 3 antagonist found in snake venom, suggested that PSG1 may be a selective alpha IIb beta 3 ligand. Here we show that human PSG1 binds alpha IIb beta 3 and inhibits the platelet - fibrinogen interaction. Unexpectedly, however, the KGD is not critical as multiple PSG1 domains independently bind and inhibit alpha IIb beta 3 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. en_US
dc.language.iso eng en_US
dc.publisher Public Library of Science en_US
dc.relation.ispartofseries PLOS one;8 (2), e57491
dc.relation.uri http://dx.doi.org/10.1371/journal.pone.0057491
dc.subject alternative activation en_US
dc.subject expression en_US
dc.subject preeclampsia en_US
dc.subject coagulation en_US
dc.subject secretion en_US
dc.subject monocytes en_US
dc.subject markers en_US
dc.subject cells en_US
dc.subject PSG en_US
dc.title Pregnancy-specific glycoproteins bind integrin alpha IIb beta 3 and inhibit the platelet-fibrinogen interaction en_US
dc.type info:eu-repo/semantics/article en_US
dc.type.supercollection all_ul_research en_US
dc.type.supercollection ul_published_reviewed en_US
dc.date.updated 2014-04-08T13:25:39Z
dc.description.version PUBLISHED
dc.rights.accessrights info:eu-repo/semantics/openAccess en_US
dc.internal.rssid 1436619
dc.internal.copyrightchecked Yes
dc.description.status peer-reviewed


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