title: Activation of Protein C in Human Trophoblasts in Culture and Downregulation of Trophoblast Endothelial Protein C Receptor by TNF-α.
abstract: In mice, trophoblasts are equipped with a potent anticoagulant mechanism, the protein C pathway. In human placenta, no functional studies of the protein C pathway are available. Human first-trimester trophoblasts (CK(++) HLA-G(+/-) Vim(-)) were isolated and kept in culture for a maximum of 48 hours. Activation of protein C on trophoblasts was at least as efficient as in endothelial cells (4.43 × 10 (-) (7) nmol/L/min/cell). Endothelial protein C receptor (EPCR) was expressed in syncytiotrophoblasts and extravillous trophoblasts. Downregulation of the messenger RNA of trophoblast EPCR occurred when trophoblasts were challenged with tumor necrosis factor α, and it could be prevented by unfractionated heparin but not by low-molecular-weight heparin at therapeutic doses. In conclusion, there is a functional protein C pathway on human first-trimester trophoblasts which can be modulated by inflammation. This finding has implications for the pathogenesis and prevention of placenta-mediated obstetric complications.
authors: Servizio di Immunoematologia e Medicina Trasfusionale, Azienda Ospedaliera San Paolo, Polo Universitario, Italy Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milano, Italy elena.faioni@unimi.it.
authors: E M
authors: EM
authors: Faioni
authors: Servizio di Immunoematologia e Medicina Trasfusionale, Azienda Ospedaliera San Paolo, Polo Universitario, Italy Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milano, Italy.
authors: G
authors: G
authors: Fontana
authors: Servizio di Immunoematologia e Medicina Trasfusionale, Azienda Ospedaliera San Paolo, Polo Universitario, Italy Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milano, Italy.
authors: C
authors: C
authors: Razzari
authors: Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milano, Italy U.O. Ostetricia e Ginecologia, Azienda Ospedaliera San Paolo, Polo Universitario, Italy.
authors: L
authors: L
authors: Avagliano
authors: Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milano, Italy U.O. Anatomia Patologica, Azienda Ospedaliera San Paolo, Polo Universitario, Italy.
authors: G
authors: G
authors: Bulfamante
authors: Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milano, Italy U.O. Ostetricia e Ginecologia, Azienda Ospedaliera San Paolo, Polo Universitario, Italy.
authors: E
authors: E
authors: Calvi
authors: Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milano, Italy U.O. Anatomia Patologica, Azienda Ospedaliera San Paolo, Polo Universitario, Italy.
authors: P
authors: P
authors: Doi
authors: Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milano, Italy U.O. Ostetricia e Ginecologia, Azienda Ospedaliera San Paolo, Polo Universitario, Italy.
authors: A M
authors: AM
authors: Marconi
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology; D015703:Antigens, CD / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D015536:Down-Regulation; D000074283:Endothelial Protein C Receptor; D004789:Enzyme Activation; D005260:Female; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011486:Protein C / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D018180:Thrombomodulin / Q000378:metabolism; D014327:Trophoblasts / Q000187:drug effects* / Q000201:enzymology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D015703:Antigens, CD; D000074283:Endothelial Protein C Receptor; C478370:PROCR protein, human; D011486:Protein C; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C546931:THBD protein, human; D018180:Thrombomodulin; D014409:Tumor Necrosis Factor-alpha; D006493:Heparin
keywords: TNF-α; heparin; protein C pathway; thrombomodulin; trophoblasts