{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T08:03:00Z","timestamp":1769846580230,"version":"3.49.0"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,6,15]],"date-time":"2012-06-15T00:00:00Z","timestamp":1339718400000},"content-version":"vor","delay-in-days":45,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:p>Lee KG, Lee H, Ha JM, Lee YK, Kang HJ, Park C\u2010G, Kim SJ. Increased human tumor necrosis factor\u2010\u03b1 levels induce procoagulant change in porcine endothelial cells in vitro. Xenotransplantation 2012; 19: 186\u2013195. \u00a9 2012 John Wiley &amp; Sons A\/S.<\/jats:p><jats:p><jats:bold>Abstract:\u2002<\/jats:bold><jats:bold> Background:\u2002<\/jats:bold> Intravascular thrombosis and systemic coagulation abnormalities are major hurdles to successful xenotransplantation and are signs of acute humoral rejection. Increased expression of tissue factor (TF) is associated with the development of microvascular thrombosis in xenografts. To develop an effective strategy to prevent accelerated coagulation in xenografts, we investigated the mechanism by which porcine endothelial cells (PECs) become procoagulant after contact with human blood.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> The changes in TF mRNA levels and activity in PECs after incubation with 20% human serum or human bioactive molecules, including C5a, tumor necrosis factor\u2010\u03b1 (TNF\u03b1) and interleukin (IL)\u20101\u03b1, were evaluated using real\u2010time PCR and the factor Xa chromogenic assay, respectively. The procoagulant changes in PECs by these agonists were evaluated by measuring the coagulation time of human citrated plasma suspended with PECs pretreated with each agonist. TF expression and coagulation times were also assessed in PECs transfected with short interfering RNA (siRNA) designed to knock down porcine TF. We also examined the production of proinflammatory cytokines in human whole\u2010blood or plasma after contact with PECs, which were screened using the cytometric bead array system. TNF\u03b1 levels were measured using ELISA in whole\u2010blood after contact with PECs, with or without the addition of xenoreactive antibodies or C1 esterase inhibitor.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> Porcine TF mRNA and activity in PECs were up\u2010regulated in response to human TNF\u03b1 and IL\u20101\u03b1 but were not affected by C5a or 20% human serum. Up\u2010regulation of TF expression by human TNF\u03b1 or IL\u20101\u03b1 shortened PEC\u2010induced coagulation time, while siRNA\u2010mediated knockdown of TF expression prolonged coagulation time. The incubation of PECs with human whole\u2010blood led to a significant increase in human TNF\u03b1 levels in the blood, which was promoted by the addition of xenoreactive antibodies and prevented by C1 esterase inhibitor.<\/jats:p><jats:p><jats:bold>Conclusions:\u2002<\/jats:bold> Human TNF\u03b1 level increases in human blood after contact with PECs, which is attributed to xenoreactive antibody binding and subsequent complement activation. Human TNF\u03b1 induces procoagulant changes in PECs with increased TF expression. This study suggests that human TNF\u03b1 may be one of the mediators linking complement activation with procoagulant changes in the xenoendothelium.<\/jats:p>","DOI":"10.1111\/j.1399-3089.2012.00704.x","type":"journal-article","created":{"date-parts":[[2012,6,15]],"date-time":"2012-06-15T15:04:14Z","timestamp":1339772654000},"page":"186-195","source":"Crossref","is-referenced-by-count":13,"title":["Increased human tumor necrosis factor\u2010\u03b1 levels induce procoagulant change in porcine endothelial cells in vitro"],"prefix":"10.1111","volume":"19","author":[{"given":"Kyoung Geun","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haneulnari","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeong Mi","family":"Ha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young 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