Tissue factor and tissue factor pathway inhibitor levels in trophoblast cells: implications for placental hemostasis

 

 Buy Article Permissions and Reprints

Summary

The placenta is a highly vascularized organ with fetal and maternal blood supply. Syncytiotrophoblasts (STB), which line the placenta villous are possibly involved in local hemostatic mechanisms.The aim of this study was to evaluate the levels of tissue factor (TF) and its inhibitors, tissue factor pathway inhibitor (TFPI,TFPI-2), in STB model within hemostatic and inflammatory environments. Human primary STB cell cultures were characterized by vascular and hormonal markers. TF and TFPI mRNA expression, protein levels and activity were determined and compared to human umbilical vein endothelial cells (HUVEC). High levels of TF were demonstrated in STB cells compared to low levels in HUVEC. In contrast, STB expressed lower TFPI levels than HUVEC. LPS and TNFα increased the high constitutive TF in STB, whereas LPS and IL-1α further reduced TFPI levels. The procoagulant tendency of STB identified by us may reflect the physiological need for immediate inhibition of hemorrhage in the placental inter-villous spaces in basal and inflammatory conditions.This hemostatic balance may be critical for normal placental function and pregnancy outcome.

• References

• 1 Brenner B, Blumenfeld Z. Thrombophilia and fetal loss. Blood Rev 1997; 11: 72-79.
  CrossrefPubMedGoogle Scholar
• 2 Lanir N, Aharon A, Brenner B. Procoagulant and anticoagulant mechanisms in human placenta. Semin Thromb Hemost 2003; 29: 175-84.
  Article in Thieme ConnectPubMedGoogle Scholar
• 3 Kuczynski J, Uszynski W, Zekanowska E. et al. Tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in the placenta and myometrium. Eur J Obstet Gynecol Reprod Biol 2002; 105: 15-19.
  CrossrefPubMedGoogle Scholar
• 4 Lockwood CJ, Krikun G, Runic R. et al. Progestin epidermal growth factor regulation of tissue factor expression during decudualization of human endometrial stromal cells. J Clin Endocrinol Metabol 2000; 85: 297-301.
  PubMedGoogle Scholar
• 5 Uszynski M, Zekanowska E, Uszynski W. et al. Tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in amniotic fluid and blood plasma: implications for the mechanism of amniotic fluid embolism. Eur J Obstet Gynecol Reprod Biol 2001; 95: 163-6.
  CrossrefPubMedGoogle Scholar
• 6 Chen J, Bierhaus A, Schiekofer S. et al. Tissue factor-a receptor involved in the control of cellular properties, including angiogenesis. Thromb Haemost 2001; 86: 334-45.
  Article in Thieme ConnectPubMedGoogle Scholar
• 7 Parry GC, Mackman N. Mouse embryogenesis requires the tissue factor extracellular domain but not the cytoplasmic domain. J Clin Invest 2000; 105: 1547-54.
  CrossrefPubMedGoogle Scholar
• 8 Carson SD, Ramsey CA. Tissue factor is present in placental microvilli and cofractionates with microvilli membrane proteins. Placenta 1985; 06: 5-12.
  CrossrefPubMedGoogle Scholar
• 9 Reverdiau P, Jarousseau AC, Thibault G. et al. Tissue factor activity of syncythiotrohoblasts plasma membranes and tumoral trophoblasts cells in culture. Thromb Haemost 1995; 73: 49-54.
  Article in Thieme ConnectPubMedGoogle Scholar
• 10 Faulk WP, Labarrere CA, Carson SD. Tissue factor: Identification and characterization of cell types in human placenta. Blood 1990; 76: 86-96.
  PubMedGoogle Scholar
• 11 Meszaros K, Aberle S, Dedrick R. et al. Monocyte tissue factor induction by lipopolysaccharide (LPS): dependence on LPS-binding protein and CD 14, and inhibition by a recombinant fragment of bactericidal/permeability-increasing protein. Blood 1994; 83: 2516-25.
  PubMedGoogle Scholar
• 12 Mattsson E, Herwald H, Bjorck L. et al. Peptidoglycan from staphylococcus aureus induces tissue factor expression and procoagulant activity in human monocytes. Infect. Immunol 2002; 70: 3033-9.
  CrossrefPubMedGoogle Scholar
• 13 Wada H, Wakita Y, Shiku H. Tissue factor expression in endothelial cells in health and disease. Blood Coagul Fibrinolysis 1995; 06: S26-31.
  CrossrefPubMedGoogle Scholar
• 14 Bajaj MS, Birktoft JJ, Steer SA, Bajaj SP. Structure and biology of tissue factor pathway inhibitor. Thromb Haemost 2001; 86: 959-72.
  Article in Thieme ConnectPubMedGoogle Scholar
• 15 Bajaj MS, Kuppuswamy MN, Manepalli AN. et al. Transcriptional expression of tissue factor pathway inhibitor, thrombomodulin and von Willebrand factor in normal human tissues. Thromb Haemost 1999; 82: 1047-52.
  Article in Thieme ConnectPubMedGoogle Scholar
• 16 Miyagi Y, Koshikawa N, Yasumitsu H. et al. cDNA cloning and mRNA expression of a serine proteinase inhibitor secreted by cancer cells: identification as placental protein 5 and tissue factor pathway inhibitor-2. J Biochem 1994; 116: 939-42.
  CrossrefPubMedGoogle Scholar
• 17 Udagawa K, Miyagi Y, Hirahara F. et al. Specific expression of PP5/TFPI2 mRNA by syncytiotrophoblasts in human placenta as revealed by in situ hybridization. Placenta 1998; 19: 217-23.
  CrossrefPubMedGoogle Scholar
• 18 Udagawa K, Yasumitsu H, Esaki M. et al. Subcellular localization of PP5/TFPI-2 in human placenta: a possible role of PP5/TFPI-2 as an anti-coagulant on the surface of syncytiotrophoblasts. Placenta 2002; 23: 145-53.
  CrossrefPubMedGoogle Scholar
• 19 Zhou Y, Fisher SJ, Janatpour M. et al. Human cytotrophoblasts adopt a vascular phenotype as they differentiate A strategy for successful endovascular invasion?. J Clin Invest 1997; 99: 2139-51.
  CrossrefPubMedGoogle Scholar
• 20 Edstrom CS, Calhoun DA, Christensen RD. Expression of tissue factor pathway inhibitor in human fetal and placental tissues. Early Hum Dev 2000; 59: 77-84.
  CrossrefPubMedGoogle Scholar
• 21 Fazel A, Vincenot A, Malassine A. et al. Increase in expression and activity of thrombomodulin in term human syncytiotrophoblast microvilli. Placenta 1998; 19: 261-8.
  CrossrefPubMedGoogle Scholar
• 22 Isermann B, Sood R, Pawlinski R. et al. The thrombomodulin-protein C system is essential for the maintenance of pregnancy. Nat Med 2003; 09: 331-7.
  CrossrefPubMedGoogle Scholar
• 23 Kliman HJ, Nestler J, Sermasi E. et al. Purification, characterization and in vitro differentiation of cytotrophoblassts from human term placentae. Endocrinology 1986; 118: 1567-81.
  CrossrefPubMedGoogle Scholar
• 24 Jaffe EA, Nachman RL, Becher GG. et al. Culture of endothelial cells derived from umbilical veins. J Clin Invest 1973; 52: 2745-56.
  CrossrefPubMedGoogle Scholar
• 25 Sandset PM, Larsen ML, Abildgaard U, Lindahl AK, Qdegaard OR. Chromogenic substrate assay of extrinsic pathway inhibitor (EPI): Levels In normal population and relation to cholesterol. Blood Coagul Fibrinolysis 1991; 02: 425-33.
  CrossrefPubMedGoogle Scholar
• 26 Iochmann S, Reverdiau MP, Beaujean S. et al. Fast detection of tissue factor and tissue factor pathway inhibitor messenger RNA in endothelial cells and monocytes by sensitive reverse transcription-polymerase chain reaction. Thromb Res 1999; 94: 165-73.
  CrossrefPubMedGoogle Scholar
• 27 Nemerson Y. Tissue factor and haemostasis. Blood 1998; 71: 1-8.
  PubMedGoogle Scholar
• 28 Potgens AJ, Schmitz U, Bose P. et al. Mechanisms of syncytial fusion. Placenta 2002; 23: S107-S113.
  CrossrefPubMedGoogle Scholar
• 29 Hubé F, Reverdiau P, Iochmann S. et al. Demonstration of a tissue factor pathway inhibitor 2 messenger RNA synthesis by pure villous cytotrophoblast cells isolated from term human placentas. Biol Reprod 2003; 68: 1888-94.
  CrossrefPubMedGoogle Scholar
• 30 Potgens AJ, Kataoka H, Ferstl S. et al. A positive immunoselection method to isolate villous cytotrophoblast cells from first trimester and term placenta to high purity. Placenta 2003; 24: 412-23.
  CrossrefPubMedGoogle Scholar
• 31 Malassine A, Cronier L. Hormones and human trophoblast differentiation: a review. Endocrine 2002; 19: 3-11.
  CrossrefPubMedGoogle Scholar
• 32 Rand JH, Wu XX. Guller Set al. Antiphosphlipid immunoglobulin G antibodies reduce annexin V levels in syncytiotrophoblast apical membranes and in culture media of placental villi. Am J Obst Gynecol 1997; 177: 918-23.
  PubMedGoogle Scholar
• 33 Aasrum M, Prydz H. Gene targeting of tissue factor, factor X and factor VII in mice, their involvement in embryonic development. Biochemistry (Mosc) 2002; 67: 25-32.
  PubMedGoogle Scholar
• 34 Lockwood CJ, Krikun G, Schatz F. The decidua regulates hemostasis in human endometrium. Semin Reprod Endocrinol 1999; 17: 45-51.
  Article in Thieme ConnectPubMedGoogle Scholar
• 35 Nemerson Y, Giesen PL. Some thoughts about localization and expression of tissue factor. Blood Coagul Fibrinolysis 1998; 09: S45-47.
  PubMedGoogle Scholar
• 36 Rauch U, Nemerson Y. Tissue factor, the blood, and the arterial wall. Trends Cardiovasc Med 2000; 10: 139-43 a.
  CrossrefPubMedGoogle Scholar
• 37 Chand HS, Schmidt AE, Bajaj SP. et al. Structure function analysis of the reactive site in the first kunitz-type domain of human tissue factor pathway inhibitor-2. J Biol Chem 2004; 79: 17500-7.
  PubMedGoogle Scholar
• 38 Herman HP, Sukhova KG, Kisiel W. et al. Tissue factor pathway inhibitor-2 is a novel inhibitor of matrix metalloproteinases with implications for atherosclerosis. J Clin Invest 2001; 107: 1117-26.
  CrossrefPubMedGoogle Scholar
• 39 Ruf W, Seftor AE, Petrovan JR. et al. Differential role of tissue factor pathway inhibitors 1 and 2 in melanoma vasculogenic mimicry. Cancer Res 2003; 63: 5381-9.
  PubMedGoogle Scholar
• 40 Konduri SD, Tasiou A, Chandrasekar N. et al. Role of tissue factor pathway inhibitor-2 (TFPI-2) in amelanotic melanoma (C-32) invasion. Clin Exp Metastasis 2000; 18: 303-8.
  CrossrefPubMedGoogle Scholar
• 41 Bowen JM, Chamley L, Mitchell MD. et al. Cytokines of the placenta and extra-placental membranes: biosynthesis, secretion and roles in establishment of pregnancy in women. Placenta 2002; 23: 239-56.
  CrossrefPubMedGoogle Scholar
• 42 Baergen R, Benirschke K, Ulich TR. Cytokine expression in the placenta. The role of interleukin 1 and interleukin 1 receptor antagonist expression in chorioamnionitis and parturition. Arch Pathol Lab Med 1994; 118: 52-5.
  PubMedGoogle Scholar
• 43 Parry GC, Mackman N. Transcriptional regulation of tissue factor expression in human endothelial cells. Arterioscler Thromb Vasc Biol 1995; 15: 612-21.
  CrossrefPubMedGoogle Scholar
• 44 Rounioja S, Rasanen J, Glumoff V. et al. Intraamniotic lipopolysaccharide leads to fetal cardiac dysfunction. A mouse model for fetal inflammatory response. Cardiovasc Res 2003; 60: 156-64.
  CrossrefPubMedGoogle Scholar
• 45 Kohmura Y, Kirikae T, Kirikae F. et al. Lipopolysaccharide (LPS)-induced intrauterine fetal death (IUFD) in mice is principally due to maternal cause but not fetal sensitivity to LPS. Microbiol Immunol 2000; 44: 897-904.
  CrossrefPubMedGoogle Scholar
• 46 Estelles A, Gilabert J, Grancha S. et al. Abnormal expression of type 1 plasminogen activator inhibitor and tissue factor in severe preeclampsia. Thromb Haemost 1998; 79: 500-8.
  Article in Thieme ConnectPubMedGoogle Scholar
• 47 Ameri A, Kuppuswamy MN, Basu S. et al. Expression of tissue factor pathway inhibitor by cultured endothelial cells in response to inflammatory mediators. Blood 1992; 79: 3219-26.
  PubMedGoogle Scholar
• 48 Speiser W, Kapiotis S, Kopp CW. et al. Effect of intradermal tumor necrosis factor-induced inflammation on coagulation factors in dermal vessel endothelium. Thromb Haemost 2001; 85: 362-7.
  Article in Thieme ConnectPubMedGoogle Scholar
• 49 Kereveur A, Enjyoji K, Masuda K. et al. Production of tissue factor pathway inhibitor in cardiomyocytes and its upregulation by interleukin-1. Thromb Haemost 2001; 86: 1314-9.
  Article in Thieme ConnectPubMedGoogle Scholar