{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:26:03Z","timestamp":1792092363879,"version":"4.4.0"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2004,12,13]],"date-time":"2004-12-13T00:00:00Z","timestamp":1102896000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2005,1]]},"abstract":"<jats:p><jats:bold>Abstract:\u2002<\/jats:bold><jats:bold> Background:\u2002<\/jats:bold> Xenograft rejection is associated with vascular inflammation, thrombocytopenia and the accelerated consumption of coagulation factors. Primary biological incompatibilities of the xenograft in the regulation of clotting appear to amplify pathological processes associated with rejection. The functional incompatibility of porcine von Willebrand factor (vWF) expressed within the xenograft vasculature may heighten interactions with the primate platelet receptor GPIb, hence augmenting formation of platelet microthrombi and vascular injury. Here, we address the functional impact of O\u2010linked glycosylation of the vWF A1 domain on primate platelet activation.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> Recombinant human or porcine vWF A1\u2010domains were transiently over\u2010expressed in COS\u20107 cells as FLAG\u2010tagged fusion protein, linked to plasma membranes via GPI anchors. O\u2010linked glycosylation was blocked by the addition of phenyl\u2010<jats:italic>\u03b1<\/jats:italic>\u2010GalNAc2 to cultures. Expressed vWF\u2010A1 domains were characterized utilizing cytofluometric\u2010 and Western blot analyses.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> Cytofluometric analysis confirmed equivalent levels of human and porcine vWF A1\u2010domain expression irrespective of the levels of O\u2010linked glycosylation. Differential glycosylation patterns of vWF\u2010A1 under these conditions were confirmed by Western blot analyses. Native porcine vWF A1\u2010domains had enhanced human platelet activation potential when compared with human recombinant vWF A1. However, the loss of O\u2010linked glycosylation abolished differences in aggregatory responses between human and porcine vWF A1 domains.<\/jats:p><jats:p><jats:bold>Conclusions:\u2002<\/jats:bold> Various degrees of O\u2010linked glycosylation of vWF\u2010A1\u2010domains modulate levels of functional interaction with platelet receptor GPIb and consequent platelet aggregation responses in vitro. These data may have implications for outcomes of xenotransplantation. We speculate that alterations in glycosylation of vWF and other adhesion proteins associated with the targeting of the <jats:italic>\u03b1<\/jats:italic>1,3\u2010Gal\u2010epitope in mutant swine may have salutatory effects on the primate platelet activation observed in these xenografts.<\/jats:p>","DOI":"10.1111\/j.1399-3089.2004.00187.x","type":"journal-article","created":{"date-parts":[[2004,12,13]],"date-time":"2004-12-13T14:27:38Z","timestamp":1102948058000},"page":"30-37","source":"Crossref","is-referenced-by-count":65,"title":["O\u2010Linked glycosylation and functional incompatibility of porcine von Willebrand factor for human platelet GPIb receptors"],"prefix":"10.1111","volume":"12","author":[{"suffix":"II","given":"Jan","family":"Schulte am Esch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon 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Characterization of O\u2010 glycosylations at serine residues 52 and 60 and effects of site\u2010 directed mutagenesis of serine 52 to alanine","volume":"266","author":"Bjoern S","year":"1991","journal-title":"J Biol Chem"},{"key":"e_1_2_15_37_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00183a021"},{"key":"e_1_2_15_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)37073-5"},{"key":"e_1_2_15_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1993.tb18361.x"},{"key":"e_1_2_15_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)42736-6"},{"key":"e_1_2_15_41_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.22.13406"},{"key":"e_1_2_15_42_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116112"},{"key":"e_1_2_15_43_2","doi-asserted-by":"crossref","first-page":"8149","DOI":"10.1016\/S0021-9258(18)92954-6","article-title":"Dimeric ristocetin flocculates proteins, binds to platelets, and mediates von Willebrand factor\u2010dependent agglutination of platelets","volume":"266","author":"Scott JP","year":"1991","journal-title":"J Biol Chem"},{"key":"e_1_2_15_44_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.17.10396"},{"key":"e_1_2_15_45_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201327200"},{"key":"e_1_2_15_46_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.107355"},{"key":"e_1_2_15_47_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1977.tb05761.x"}],"container-title":["Xenotransplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1399-3089.2004.00187.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1399-3089.2004.00187.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T23:53:17Z","timestamp":1696895597000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1399-3089.2004.00187.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,12,13]]},"references-count":46,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2005,1]]}},"alternative-id":["10.1111\/j.1399-3089.2004.00187.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1399-3089.2004.00187.x","archive":["Portico"],"relation":{},"ISSN":["0908-665X","1399-3089"],"issn-type":[{"value":"0908-665X","type":"print"},{"value":"1399-3089","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,12,13]]}}}