N Mackman

Summary

Affiliation: The Scripps Research Institute
Country: USA

Publications

  1. ncbi request reprint Gene targeting in hemostasis. tissue factor
    N Mackman
    The Scripps Research Institute, Depts of Immunology and Vascular Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Front Biosci 6:D208-15. 2001
  2. ncbi request reprint Lipopolysaccharide induction of gene expression in human monocytic cells
    N Mackman
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Immunol Res 21:247-51. 2000
  3. ncbi request reprint Role of tissue factor in hemostasis, thrombosis, and vascular development
    Nigel Mackman
    The Scripps Research Institute, Department of Immunology, 10550 North Torrey Pines Road, La Jolla, Calif 92037, USA
    Arterioscler Thromb Vasc Biol 24:1015-22. 2004
  4. ncbi request reprint Role of tissue factor in hemostasis and thrombosis
    Nigel Mackman
    Departments of Immunology and Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, CVN 18, La Jolla, CA 92037, USA
    Blood Cells Mol Dis 36:104-7. 2006
  5. ncbi request reprint Role of the extrinsic pathway of blood coagulation in hemostasis and thrombosis
    Nigel Mackman
    Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, Mail Code SP30 3040, La Jolla, CA 92037, USA
    Arterioscler Thromb Vasc Biol 27:1687-93. 2007
  6. ncbi request reprint Tissue-specific hemostasis in mice
    Nigel Mackman
    Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA
    Arterioscler Thromb Vasc Biol 25:2273-81. 2005
  7. ncbi request reprint Regulation of the tissue factor gene
    N Mackman
    Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA
    Thromb Haemost 78:747-54. 1997
  8. ncbi request reprint Lipopolysaccharide activation of the MEK-ERK1/2 pathway in human monocytic cells mediates tissue factor and tumor necrosis factor alpha expression by inducing Elk-1 phosphorylation and Egr-1 expression
    M Guha
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Blood 98:1429-39. 2001
  9. pmc Inhibition of the tissue factor-thrombin pathway limits infarct size after myocardial ischemia-reperfusion injury by reducing inflammation
    J H Erlich
    Scripps Research Institute, La Jolla, California Seattle, Washington Dresden, Germany
    Am J Pathol 157:1849-62. 2000
  10. ncbi request reprint Role of cardiac myocyte tissue factor in heart hemostasis
    R Pawlinski
    Department of Immunology, The Scripps Research Institute, La Jolla, CA, USA
    J Thromb Haemost 5:1693-700. 2007

Research Grants

  1. Role of PAR-1 and PAR-2 in Cardiac Remodeling
    Nigel Mackman; Fiscal Year: 2007

Collaborators

Detail Information

Publications85

  1. ncbi request reprint Gene targeting in hemostasis. tissue factor
    N Mackman
    The Scripps Research Institute, Depts of Immunology and Vascular Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Front Biosci 6:D208-15. 2001
    ..Indeed, gene targeting of TF resulted in embryonic lethality, which appeared to be due to a defect in the yolk sac vasculature...
  2. ncbi request reprint Lipopolysaccharide induction of gene expression in human monocytic cells
    N Mackman
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Immunol Res 21:247-51. 2000
    ..Inhibition of these signaling pathways provides a novel therapeutic approach to prevent inducible gene expression in monocytes...
  3. ncbi request reprint Role of tissue factor in hemostasis, thrombosis, and vascular development
    Nigel Mackman
    The Scripps Research Institute, Department of Immunology, 10550 North Torrey Pines Road, La Jolla, Calif 92037, USA
    Arterioscler Thromb Vasc Biol 24:1015-22. 2004
    ..This review focuses on the roles of TF in hemostasis, thrombosis, and vascular development...
  4. ncbi request reprint Role of tissue factor in hemostasis and thrombosis
    Nigel Mackman
    Departments of Immunology and Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, CVN 18, La Jolla, CA 92037, USA
    Blood Cells Mol Dis 36:104-7. 2006
    ..Inhibition of TF activity in patients with TF expression in vascular cells and with elevated levels of circulating TF may decrease thrombosis associated with a variety of diseases...
  5. ncbi request reprint Role of the extrinsic pathway of blood coagulation in hemostasis and thrombosis
    Nigel Mackman
    Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, Mail Code SP30 3040, La Jolla, CA 92037, USA
    Arterioscler Thromb Vasc Biol 27:1687-93. 2007
    ..Understanding how the extrinsic pathway of blood coagulation contributes to hemostasis and thrombosis may lead to the development of safe and effective hemostatic agents and antithrombotic drugs...
  6. ncbi request reprint Tissue-specific hemostasis in mice
    Nigel Mackman
    Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA
    Arterioscler Thromb Vasc Biol 25:2273-81. 2005
    ..These observations, together with the phenotypes of mice that have defects in the procoagulant, anticoagulant, and fibrinolytic pathways, indicate that hemostasis is regulated in a tissue-specific manner...
  7. ncbi request reprint Regulation of the tissue factor gene
    N Mackman
    Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA
    Thromb Haemost 78:747-54. 1997
    ..These results suggest that cell type-specific pathways regulate TF gene expression...
  8. ncbi request reprint Lipopolysaccharide activation of the MEK-ERK1/2 pathway in human monocytic cells mediates tissue factor and tumor necrosis factor alpha expression by inducing Elk-1 phosphorylation and Egr-1 expression
    M Guha
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Blood 98:1429-39. 2001
    ..The data indicate that LPS induction of Egr-1 gene expression is required for maximal induction of the TNF-alpha and TF genes in human monocytic cells...
  9. pmc Inhibition of the tissue factor-thrombin pathway limits infarct size after myocardial ischemia-reperfusion injury by reducing inflammation
    J H Erlich
    Scripps Research Institute, La Jolla, California Seattle, Washington Dresden, Germany
    Am J Pathol 157:1849-62. 2000
    ..We propose that cardiomyocyte TF initiates extravascular thrombin generation, which enhances inflammation and injury during myocardial I/R...
  10. ncbi request reprint Role of cardiac myocyte tissue factor in heart hemostasis
    R Pawlinski
    Department of Immunology, The Scripps Research Institute, La Jolla, CA, USA
    J Thromb Haemost 5:1693-700. 2007
    ..Hemosiderosis and fibrosis are observed in the hearts of all low TF mice as early as 3 months of age. In contrast, TF(+/-) mice expressing approximately 50% of wild-type levels of TF had no detectable hemostatic defects...
  11. ncbi request reprint Regulation of the tissue factor gene in human monocytic cells. Role of AP-1, NF-kappa B/Rel, and Sp1 proteins in uninduced and lipopolysaccharide-induced expression
    P Oeth
    Department of Immunology, Scripps Research Institute, La Jolla, Calif 92037, USA
    Arterioscler Thromb Vasc Biol 17:365-74. 1997
    ..These data indicated that c-Fos/c-Jun, c-Rel/p65, and Sp1 regulate TF gene expression in human monocytic cells...
  12. pmc Tissue factor is required for uterine hemostasis and maintenance of the placental labyrinth during gestation
    J Erlich
    Departments of Immunology and Vascular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 96:8138-43. 1999
    ..This study demonstrated that TF is required for uterine hemostasis and revealed an unexpected role of TF in the maintenance of the placental labyrinth...
  13. ncbi request reprint LPS induction of gene expression in human monocytes
    M Guha
    Departments of Immunology, C-204, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Cell Signal 13:85-94. 2001
    ..These signaling pathways in turn activate a variety of transcription factors that include NF-kappaB (p50/p65) and AP-1 (c-Fos/c-Jun), which coordinate the induction of many genes encoding inflammatory mediators...
  14. pmc Tissue factor deficiency causes cardiac fibrosis and left ventricular dysfunction
    R Pawlinski
    Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 99:15333-8. 2002
    ..We propose that TF expression by cardiac myocytes provides a secondary hemostatic barrier to protect the heart from hemorrhage...
  15. pmc RelB modulation of IkappaBalpha stability as a mechanism of transcription suppression of interleukin-1alpha (IL-1alpha), IL-1beta, and tumor necrosis factor alpha in fibroblasts
    Y Xia
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    Mol Cell Biol 19:7688-96. 1999
    ..Our findings suggest a novel transcription suppression function of RelB in fibroblasts...
  16. ncbi request reprint Tissue factor in the heart. Multiple roles in hemostasis, thrombosis, and inflammation
    T Luther
    Scripps Research Institute, La Jolla, CA 92037, USA
    Trends Cardiovasc Med 11:307-12. 2001
    ..This review discusses the roles of TF in hemostasis, thrombosis, and inflammation in the heart as well as other potential roles of TF in the maintenance of cardiac muscle...
  17. ncbi request reprint Complete sequence of the human tissue factor gene, a highly regulated cellular receptor that initiates the coagulation protease cascade
    N Mackman
    Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037
    Biochemistry 28:1755-62. 1989
    ..These factors included AP-1 and AP-2 which can mediate the effects of phorbol esters, agonists known to induce TF expression in monocytes and vascular endothelial cells...
  18. ncbi request reprint Toll-like receptor 2-mediated NF-kappa B activation requires a Rac1-dependent pathway
    L Arbibe
    Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA
    Nat Immunol 1:533-40. 2000
    ..Thus Rac1 controls a second, I kappa B-independent, pathway to NF-kappa B activation and is essential in innate immune cell signaling via TLR2...
  19. ncbi request reprint Transcriptional regulation of the tissue factor gene in human epithelial cells is mediated by Sp1 and EGR-1
    M Z Cui
    Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 271:2731-9. 1996
    ..These data indicated that TF gene expression in HeLa cells was regulated by both Sp1 and EGR-1...
  20. ncbi request reprint Protease inhibitors block lipopolysaccharide induction of tissue factor gene expression in human monocytic cells by preventing activation of c-Rel/p65 heterodimers
    N Mackman
    Department of Immunology, Scripps Research Institute, La Jolla, California 92037
    J Biol Chem 269:26363-7. 1994
    ..Taken together, these data indicated that inhibiting nuclear translocation of c-Rel/p65 heterodimers prevented LPS induction of TF gene transcription in monocytic cells...
  21. pmc Functional analysis of the human tissue factor promoter and induction by serum
    N Mackman
    Department of Immunology, Research Institute of Scripps Clinic, La Jolla, CA 92037
    Proc Natl Acad Sci U S A 87:2254-8. 1990
    ..Based on this functional map, we propose that the elaborate pattern of TF expression by cells results from a relatively complex promoter...
  22. ncbi request reprint A balance between tissue factor and tissue factor pathway inhibitor is required for embryonic development and hemostasis in adult mice
    Brian Pedersen
    Department of Immunology, The Scripps Research Institute, 10550 N Torrey Pines Rd, CVN 18, La Jolla, CA 92037, USA
    Blood 105:2777-82. 2005
    ..These results indicate that the correct balance between TF and TFPI in different organs is required to maintain hemostasis during embryonic development and in adult mice...
  23. pmc Regulation of an essential innate immune response by the p50 subunit of NF-kappaB
    J Bohuslav
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Clin Invest 102:1645-52. 1998
    ..Thus, p50 expression plays a key role in the development of LPS tolerance...
  24. ncbi request reprint Role of cyclic AMP response element-binding protein in cyclic AMP inhibition of NF-kappaB-mediated transcription
    G C Parry
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Immunol 159:5450-6. 1997
    ..These results suggest that activation of the protein kinase A pathway inhibits NF-kappaB transcription by phosphorylating CREB, which competes with p65 for limiting amounts of CBP...
  25. pmc Low levels of tissue factor are compatible with development and hemostasis in mice
    G C Parry
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Clin Invest 101:560-9. 1998
    ..These studies establish a novel mouse model system that can be used to examine the regulation of the human TF gene in vivo and the impact of low TF levels on the hemostatic balance in various thrombotic diseases...
  26. pmc Protease-activated receptor-1 contributes to cardiac remodeling and hypertrophy
    Rafal Pawlinski
    The Scripps Research Institute, Department of Immunology, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
    Circulation 116:2298-306. 2007
    ..The purpose of the present study was to investigate the role of PAR-1 in infarction, cardiac remodeling, and hypertrophy after I/R injury. In addition, we analyzed the effect of overexpression of PAR-1 on cardiomyocytes...
  27. ncbi request reprint Retinoic acid selectively inhibits lipopolysaccharide induction of tissue factor gene expression in human monocytes
    P Oeth
    Department of Immunology, The Scripps Research Institute, La Jolla, CA, USA
    Blood 91:2857-65. 1998
    ..Our results demonstrate that ATRA selectively inhibited LPS-induced TF gene transcription in human monocytic cells by a mechanism that does not involve repression of AP-1- or NF-kappaB-mediated transcription...
  28. pmc Mouse embryogenesis requires the tissue factor extracellular domain but not the cytoplasmic domain
    G C Parry
    Departments of Immunology and Vascular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Clin Invest 105:1547-54. 2000
    ..We propose that TF/FVIIa-dependent extracellular protease activity is required for embryogenesis...
  29. ncbi request reprint The synthetic pentasaccharide fondaparinux reduces coagulation, inflammation and neutrophil accumulation in kidney ischemia-reperfusion injury
    R D Frank
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Thromb Haemost 3:531-40. 2005
    ..Our data suggest that fondaparinux reduces kidney I/R injury primarily by inhibiting the recruitment of neutrophils...
  30. pmc Role of tissue factor and protease-activated receptors in a mouse model of endotoxemia
    Rafal Pawlinski
    Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Rd, La Jolla, CA 92037, USA
    Blood 103:1342-7. 2004
    ..These data demonstrate that hematopoietic cells are the major pathologic site of TF expression during endotoxemia and suggest that multiple protease-activated receptors mediate crosstalk between coagulation and inflammation...
  31. pmc Factor Xa binding to annexin 2 mediates signal transduction via protease-activated receptor 1
    Gourab Bhattacharjee
    Scripps Research Institute, SP 258, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
    Circ Res 102:457-64. 2008
    ..We propose that annexin 2 serves to regulate factor Xa signaling specifically in the absence of cell surface TF and may thus play physiological or pathological roles when factor Xa is generated in a TF-depleted environment...
  32. ncbi request reprint Regulation of tissue factor--mediated initiation of the coagulation cascade by cell surface grp78
    Gourab Bhattacharjee
    Department of Immunology, The Scripps Research Institute, SP258, La Jolla, CA 92037, USA
    Arterioscler Thromb Vasc Biol 25:1737-43. 2005
    ..To test the hypothesis that Grp78 negatively regulates cell surface tissue factor (TF) procoagulant activity and whether this is mediated by physical interaction...
  33. ncbi request reprint The role of the tissue factor-thrombin pathway in cardiac ischemia-reperfusion injury
    Nigel Mackman
    Departments of Immunology and Cell Biology, The Scripps Research Institute, La Jolla 92037, CA, USA
    Semin Vasc Med 3:193-8. 2003
    ..Anti-TF therapy would inhibit both thrombin-dependent fibrin deposition and thrombin-dependent PAR-1 signaling...
  34. ncbi request reprint Regulation of the tissue factor gene
    N Mackman
    Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA
    FASEB J 9:883-9. 1995
    ..Sp1 also mediates basal promoter activity. Thus, TF gene expression is complex and is regulated by a number of transcription factors that bind to distinct regions of the TF promoter...
  35. ncbi request reprint Binding of human single chain urokinase to Chinese Hamster Ovary cells and cloning of hamster u-PAR
    B Fowler
    Department of Vascular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Thromb Haemost 80:148-54. 1998
    ..In addition, the results of our studies suggest that the hamster may be a useful small animal model for studies of human urokinase function...
  36. ncbi request reprint Structure of the murine tissue factor gene. Chromosome location and conservation of regulatory elements in the promoter
    N Mackman
    Department of Immunology, Scripps Research Institute, La Jolla, CA 92037
    Arterioscler Thromb 12:474-83. 1992
    ....
  37. ncbi request reprint Conservation of tissue factor primary sequence among three mammalian species
    B S Andrews
    Department of Immunology, Research Institute of Scripps Clinic, La Jolla, CA 92037
    Gene 98:265-9. 1991
    ....
  38. ncbi request reprint A non-anticoagulant synthetic pentasaccharide reduces inflammation in a murine model of kidney ischemia-reperfusion injury
    Rolf Dario Frank
    Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Thromb Haemost 96:802-6. 2006
    ..These findings indicate that the anti-inflammatory activity of fondaparinux can be dissociated from its anticoagulant activity and that NAC-pentasaccharide is protective in kidney I/R injury...
  39. ncbi request reprint Atherosclerosis in mice is not affected by a reduction in tissue factor expression
    Rachel E Tilley
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    Arterioscler Thromb Vasc Biol 26:555-62. 2006
    ..To determine whether tissue factor (TF) contributes to the progression of atherosclerotic lesions in mice...
  40. ncbi request reprint Tissue factor in hemostasis and thrombosis
    Rachel Tilley
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    Semin Thromb Hemost 32:5-10. 2006
    ..TF expression in these diseases is associated with thrombotic events. Future therapeutic strategies may prove beneficial in the treatment of thrombosis. However, these strategies should be designed to avoid compromising hemostasis...
  41. ncbi request reprint Role of tissue factor in haemostasis, thrombosis, angiogenesis and inflammation: lessons from low tissue factor mice
    Rafal Pawlinski
    The Scripps Research Institute, 10550 North Torrey Pines Road, CVN 18, La Jolla, CA 92017, USA
    Thromb Haemost 92:444-50. 2004
    ..Low TF mice are also a useful tool to study the role of TF and the coagulation cascade in other processes, such as thrombosis, inflammation and angiogenesis...
  42. ncbi request reprint Tissue factor, coagulation proteases, and protease-activated receptors in endotoxemia and sepsis
    Rafal Pawlinski
    Departments of Immunology and Cell Biology, The Scripps Research Institute, La Jolla, CA, USA
    Crit Care Med 32:S293-7. 2004
    ..Taken together, our results suggest that activation of multiple PARs by coagulation proteases enhances inflammation during endotoxemia...
  43. pmc Genetic analysis of the role of the PI3K-Akt pathway in lipopolysaccharide-induced cytokine and tissue factor gene expression in monocytes/macrophages
    James P Luyendyk
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Immunol 180:4218-26. 2008
    ..Taken together, our results indicate that the PI3K-Akt pathway negatively regulates LPS signaling and gene expression in monocytes/macrophages...
  44. ncbi request reprint HIF-1alpha is essential for myeloid cell-mediated inflammation
    Thorsten Cramer
    Molecular Biology Section, Division of Biological Sciences, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    Cell 112:645-57. 2003
    ..This role for HIF-1alpha demonstrates its direct regulation of survival and function in the inflammatory microenvironment...
  45. ncbi request reprint PI3K-Akt pathway suppresses coagulation and inflammation in endotoxemic mice
    Gernot Schabbauer
    Department of Immunology, The Scripps Research Institute, La Jolla, Calif 92037, USA
    Arterioscler Thromb Vasc Biol 24:1963-9. 2004
    ..In this study, we analyzed the role of the phosphoinositide 3-kinase (PI3K)-Akt pathway in the activation of coagulation and the innate immune response in a mouse model of endotoxemia...
  46. pmc Tissue factor activity is increased in a combined platelet and microparticle sample from cancer patients
    Rachel E Tilley
    Department of Immunology, The Scripps Research Institute, La Jolla, CA, USA
    Thromb Res 122:604-9. 2008
    ..Of these two measurements, TF activity is considered superior to TF antigen levels because the activity more closely reflects the ability of TF to initiate coagulation. Recent studies showed that platelets also express TF...
  47. ncbi request reprint Genetic susceptibility to thrombosis
    James P Luyendyk
    Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, CVN 18, La Jolla, CA 92037, USA
    Curr Atheroscler Rep 8:193-7. 2006
    ..Tissue factor is the primary cellular initiator of blood coagulation and is a major contributor to thrombosis. In this review, we discuss the association between various polymorphisms and the risk for thrombosis...
  48. ncbi request reprint A novel class of antioxidants inhibit LPS induction of tissue factor by selective inhibition of the activation of ASK1 and MAP kinases
    James P Luyendyk
    Department of Immunology, e Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Arterioscler Thromb Vasc Biol 27:1857-63. 2007
    ..The purpose of this study was to elucidate the mechanism by which 2 structurally-related antioxidants (AGI-1067 and AGI-1095) inhibit LPS induction of tissue factor (TF) expression in human monocytic cells and endothelial cells...
  49. ncbi request reprint Regulation of tissue factor and inflammatory mediators by Egr-1 in a mouse endotoxemia model
    Rafal Pawlinski
    Department of Immunology, The Scripps Research Institute, La Jolla, CA, USA
    Blood 101:3940-7. 2003
    ..However, Egr-1 does contribute to the sustained expression of inflammatory mediators and to the maximal expression of TF at 8 hours in the kidneys and lungs...
  50. pmc Use of mouse models to study the role of tissue factor in tumor biology
    Rafal Pawlinski
    Department of Immunology, The Scripps Research Institute, La Jolla, California, USA
    Semin Thromb Hemost 34:182-6. 2008
    ..The role of host TF in tumor progression is less clear. Recently developed mouse models with altered levels of TF may be useful in further analysis of the role of host cell TF in cancer...
  51. ncbi request reprint TLR2 is constitutively expressed within the kidney and participates in ischemic renal injury through both MyD88-dependent and -independent pathways
    Alana A Shigeoka
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Immunol 178:6252-8. 2007
    ..We conclude that TLR2 protein is constitutively expressed in the kidney and plays an important role in the pathogenesis of acute ischemic injury by signaling both MyD88-dependent and MyD88-independent pathways...
  52. ncbi request reprint Dexamethasone enhances LPS induction of tissue factor expression in human monocytic cells by increasing tissue factor mRNA stability
    K Veera Reddy
    Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, CVN 18, La Jolla, CA 92037, USA
    J Leukoc Biol 76:145-51. 2004
    ..Therefore, despite an inhibition of TF gene transcription, Dex enhances TF expression in human monocytic cells by increasing the stability of TF mRNA...
  53. ncbi request reprint The phosphatidylinositol 3-kinase-Akt pathway limits lipopolysaccharide activation of signaling pathways and expression of inflammatory mediators in human monocytic cells
    Mausumee Guha
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 277:32124-32. 2002
    ..Our study provides new insight into the inhibitory mechanism by which the PI3K-Akt pathway ensures transient expression of these potent inflammatory mediators...
  54. pmc Neutrophil activation by the tissue factor/Factor VIIa/PAR2 axis mediates fetal death in a mouse model of antiphospholipid syndrome
    Patricia Redecha
    Hospital for Special Surgery, Weill Medical College of Cornell University, New York, New York, USA
    J Clin Invest 118:3453-61. 2008
    ..Our results suggest that TF/FVIIa/PAR2 signaling mediates neutrophil activation and fetal death in APS and that statins may be a good treatment for women with aPL-induced pregnancy complications...
  55. pmc Contribution of host-derived tissue factor to tumor neovascularization
    Joanne Yu
    Henderson Research Centre, McMaster University, Hamilton, ON, Canada
    Arterioscler Thromb Vasc Biol 28:1975-81. 2008
    ..The role of host-derived tissue factor (TF) in tumor growth, angiogenesis, and metastasis has hitherto been unclear and was investigated in this study...
  56. pmc Tissue factor: a link between C5a and neutrophil activation in antiphospholipid antibody induced fetal injury
    Patricia Redecha
    Hospital for Special Surgery, Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA
    Blood 110:2423-31. 2007
    ..The identification of TF as an important mediator of C5a-induced oxidative burst in neutrophils in aPL-induced fetal injury provides a new target for therapy to prevent pregnancy loss in the antiphospholipid syndrome...
  57. ncbi request reprint Role of the coagulation system in acetaminophen-induced hepatotoxicity in mice
    Patricia E Ganey
    Department of Pharmacology and Toxicology, National Food Safety and Toxicology Center, Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824, USA
    Hepatology 46:1177-86. 2007
    ..CONCLUSION: Activation of the coagulation system and PAR-1 signaling contribute significantly to APAP-induced liver injury...
  58. ncbi request reprint The development of cardiac fibrosis in low tissue factor mice is gender-dependent and is associated with differential regulation of urokinase plasminogen activator
    Darren R Davis
    Renal Research Laboratory, University of New South Wales, Level 2, Clinical Sciences Building, Prince of Wales Hospital, Randwick, NSW 2031, Australia
    J Mol Cell Cardiol 42:559-71. 2007
    ..This suggests that the down-regulation of uPA in female low-TF mice protects them from more severe cardiac fibrosis...
  59. pmc COX-2 suppresses tissue factor expression via endocannabinoid-directed PPARdelta activation
    Mallika Ghosh
    Center for Vascular Biology, Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030, USA
    J Exp Med 204:2053-61. 2007
    ..Furthermore, PPARdelta agonists may be used therapeutically to suppress coxib-induced cardiovascular side effects...
  60. pmc Signal-dependent splicing of tissue factor pre-mRNA modulates the thrombogenicity of human platelets
    Hansjorg Schwertz
    Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112, USA
    J Exp Med 203:2433-40. 2006
    ..We propose that platelet-derived TF contributes to the propagation and stabilization of a thrombus...
  61. ncbi request reprint Tissue factor deficiency and PAR-1 deficiency are protective against renal ischemia reperfusion injury
    Jacob Sevastos
    Prince of Wales Clinical School, University of New South Wales, Sydney, and Prince of Wales Hospital, Barker St, Randwick, NSW 2031, Australia
    Blood 109:577-83. 2007
    ..These experiments indicate that increased TF activity after renal IR leads to increased CXC chemokine expression and subsequent neutrophil-mediated injury predominantly by thrombin-dependent PAR-1 signaling...
  62. ncbi request reprint Mouse models in haemostasis and thrombosis
    Nigel Mackman
    Thromb Haemost 92:440-3. 2004
  63. ncbi request reprint Macrovascular thrombosis is driven by tissue factor derived primarily from the blood vessel wall
    Sharlene M Day
    Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Blood 105:192-8. 2005
    ..Therefore, our results suggest that thrombus formation in the arterial and venous macrovasculature is driven primarily by TF derived from the blood vessel wall as opposed to leukocytes...
  64. ncbi request reprint Hematopoietic cell-derived microparticle tissue factor contributes to fibrin formation during thrombus propagation
    Janet Chou
    Center for Hemostasis and Thrombosis Research, Vascular Biology Center, 330 Brookline Ave, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
    Blood 104:3190-7. 2004
    ..This demonstrates that blood-borne TF associated with hematopoietic cell-derived microparticles contributes to thrombus propagation...
  65. ncbi request reprint Mice deficient in tissue factor demonstrate attenuated intimal hyperplasia in response to vascular injury and decreased smooth muscle cell migration
    Robert T Pyo
    The Cardiovascular Institute and Department of Medicine, Mount Sinai Center, New York, New York, USA
    Thromb Haemost 92:451-8. 2004
    ..These data suggest that TF may mediate intimal hyperplasia by regulating smooth muscle cell migration...
  66. ncbi request reprint Tissue factor and thrombin mediate myocardial ischemia-reperfusion injury
    Albert J Chong
    Division of Cardiothoracic Surgery, The University of Washington, Seattle, Washington 98104, USA
    Ann Thorac Surg 75:S649-55. 2003
    ..However, defibrinogenating rabbits with ancrod had no effect on infarct size, suggesting a requirement of thrombin generation but not fibrin deposition in myocardial I/R injury...
  67. ncbi request reprint Potent inhibition of thrombin with a monoclonal antibody against tissue factor (Sunol-cH36): results of the PROXIMATE-TIMI 27 trial
    David A Morrow
    TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women s Hospital, 75 Francis Street, Boston, MA 02115, USA
    Eur Heart J 26:682-8. 2005
    ..Sunol-cH36, a chimaeric monoclonal antibody to TF, blocks binding of factor X to the TF:VIIa complex. This report describes the first completed trial of Sunol-cH36 in humans...
  68. ncbi request reprint The thrombomodulin-protein C system is essential for the maintenance of pregnancy
    Berend Isermann
    Blood Research Institute, The Blood Center of Southeastern Wisconsin, Milwaukee, Wisconsin, USA
    Nat Med 9:331-7. 2003
    ..These findings show a new function for the thrombomodulin-protein C system in controlling the growth and survival of trophoblast cells in the placenta. This function is essential for the maintenance of pregnancy...
  69. ncbi request reprint Alternatively spliced tissue factor - one cut too many?
    Nigel Mackman
    Thromb Haemost 97:5-8. 2007
  70. pmc Triggers, targets and treatments for thrombosis
    Nigel Mackman
    Division of Hematology Oncology, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Nature 451:914-8. 2008
    ..The pathogenic changes that occur in the blood vessel wall and in the blood itself resulting in thrombosis are not fully understood. Understanding these processes is crucial for developing safer and more effective antithrombotic drugs...
  71. pmc Protein disulfide isomerase acts as an injury response signal that enhances fibrin generation via tissue factor activation
    Christoph Reinhardt
    Vaskuläre Biologie und Hämostase, Institut fur Klinische Chemie, Ludwig Maximilians Universitat, Munich, Germany
    J Clin Invest 118:1110-22. 2008
    ..Our findings suggest that disulfide isomerases can act as injury response signals that trigger the activation of fibrin formation following vessel injury...
  72. pmc Early growth response gene-1 regulates hypoxia-induced expression of tissue factor in glioblastoma multiforme through hypoxia-inducible factor-1-independent mechanisms
    Yuan Rong
    Department of Pathology and Laboratory Medicine, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Cancer Res 66:7067-74. 2006
    ..We conclude that hypoxic up-regulation of tissue factor in glioblastoma multiforme cells depends largely on Egr-1 and is independent of HIF-1...
  73. pmc TLR4/CD14-mediated PI3K activation is an essential component of interferon-dependent VSV resistance in macrophages
    Gernot Schabbauer
    Department for Vascular Biology, Center for Biomolecular Medicine and Pharmacology, Medical University Vienna, Schwarzspanierstrasse 17, Vienna, Austria
    Mol Immunol 45:2790-6. 2008
    ....
  74. ncbi request reprint Does tissue factor expression by vascular smooth muscle cells provide a link between C-reactive protein and cardiovascular disease?
    Nigel Mackman
    Arterioscler Thromb Vasc Biol 28:601-3. 2008
  75. ncbi request reprint Chlamydia pneumoniae induces tissue factor expression in mouse macrophages via activation of Egr-1 and the MEK-ERK1/2 pathway
    Florian Bea
    Department of Pathobiology, University of Washington, Seattle, Wash 98195, USA
    Circ Res 92:394-401. 2003
    ..In conclusion, the C pneumoniae-induced increase in TF expression in macrophages is mediated in part by Egr-1, signaling through TLR4, and activation of the MEK-ERK1/2 pathway...
  76. ncbi request reprint Effects of enalapril on disseminated intravascular thrombin formation during systemic inflammation
    Claudia Marsik
    Department of Clinical Pharmacology, Vienna University, Vienna, Austria
    Cardiovasc Res 60:131-5. 2003
    ..Tissue factor (TF), the main trigger of coagulation is important in the propagation of cardiovascular diseases. Based on an in vitro study, we hypothesised that enalapril may blunt the endotoxin-induced, TF-triggered coagulation in humans...
  77. ncbi request reprint PML/RARalpha plays a role for basal activity and retinoid-induced repression of the tissue factor promoter in acute promyelocytic leukemia cells
    Taavo Tenno
    Department of Medical Sciences, Clinical Chemistry, Laboratory for Coagulation Research, University Hospital, SE 751 85 Uppsala, Sweden
    Thromb Haemost 90:930-9. 2003
    ..These data indicate that TF expression in APL cells is exacerbated by the presence of the PML/RARalpha fusion protein, and implicates the loss of Fos/Jun binding to the TF promoter in ATRA-induced suppression of TF...
  78. ncbi request reprint How do oxidized phospholipids inhibit LPS signaling?
    Nigel Mackman
    Arterioscler Thromb Vasc Biol 23:1133-6. 2003
  79. pmc Endotoxemia and sepsis mortality reduction by non-anticoagulant activated protein C
    Edward J Kerschen
    Blood Research Institute, Milwaukee, WI 53226, USA
    J Exp Med 204:2439-48. 2007
    ....
  80. ncbi request reprint Validation of a novel tissue factor assay in experimental human endotoxemia
    Claudia Marsik
    Department of Clinical Pharmacology, School of Medicine and Institute for Medical and Chemical Laboratory Diagnostics, Vienna University, Waehringer Guertel 18 20, A 1090 Vienna, Austria
    Thromb Res 111:311-5. 2003
    ..No point-of-care assays are currently available to measure the level of TF activity in whole blood. The current study examined the suitability of the TiFaCT assay as a point-of-care assay to detect TF expression...
  81. ncbi request reprint Oncogenic events regulate tissue factor expression in colorectal cancer cells: implications for tumor progression and angiogenesis
    Joanne L Yu
    Henderson Research Centre, Experimental Thrombosis Research, McMaster University, Hamilton, ON, Canada L8V 1C3
    Blood 105:1734-41. 2005
    ..Thus, this study establishes a causal link between cancer coagulopathy, angiogenesis, and genetic tumor progression...
  82. ncbi request reprint Interleukin-10 suppresses tissue factor expression in lipopolysaccharide-stimulated macrophages via inhibition of Egr-1 and a serum response element/MEK-ERK1/2 pathway
    Motohiro Kamimura
    Department Internal Medicine III, University of Heidelberg, Heidelberg, Germany
    Circ Res 97:305-13. 2005
    ..Taken together, these results demonstrate a pathway for the IL-10 mediated inhibition of TF expression during inflammation and may explain the antiatherosclerotic effects of IL-10...
  83. ncbi request reprint Postprandial elevation of tissue factor antigen in the blood of healthy adults
    Deborah D Motton
    Division of Endocrinology, Clinical Nutrition and Vascular Medicine, Department of Internal Medicine, Suite 5303, Genomics and Biomedical Sciences Facility, University of California, Davis, California 95616, USA
    Thromb Haemost 94:504-9. 2005
    ..These results demonstrate increased tissue factor levels in individuals who consumed a moderate fat diet. This suggests that the typical western diet may play a larger role in cardiovascular disease than merely altering lipid profiles...
  84. ncbi request reprint Oncogenes, trousseau syndrome, and cancer-related changes in the coagulome of mice and humans
    Janusz Rak
    Montreal Children s Hospital Research Institute, McGill University, Montreal, Quebec, Canada
    Cancer Res 66:10643-6. 2006
    ....
  85. ncbi request reprint Induction of tissue factor expression in human endothelial cells by CD40 ligand is mediated via activator protein 1, nuclear factor kappa B, and Egr-1
    Udo Bavendiek
    Leducq Center for Cardiovascular Research, Cardiovascular Division, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 277:25032-9. 2002
    ....

Research Grants1

  1. Role of PAR-1 and PAR-2 in Cardiac Remodeling
    Nigel Mackman; Fiscal Year: 2007
    ..The results may lead to the development of PAR-1 and PAR-2 inhibitors that may be used as novel therapies for the treatment of pathological cardiac remodeling and hypertrophy in humans. ..