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Thromb Haemost 1998; 80(06): 1008-1041
DOI: 10.1055/s-0037-1615402
Letters to the Editor
Schattauer GmbH

Activated Platelets Induce Tissue Factor Expression on Human Umbilical Vein Endothelial Cells by Ligation of CD40

Joseph R. Slupsky
1   Haemostasis Research Unit, Max-Planck-Institute for Physiological and Clinical Research, Kerckhoff-Klinik GmbH, Bad Nauheim, Germany
,
Matthias Kalbas
1   Haemostasis Research Unit, Max-Planck-Institute for Physiological and Clinical Research, Kerckhoff-Klinik GmbH, Bad Nauheim, Germany
,
Antje Willuweit
1   Haemostasis Research Unit, Max-Planck-Institute for Physiological and Clinical Research, Kerckhoff-Klinik GmbH, Bad Nauheim, Germany
,
Volker Henn
2   Molecular Immunology, Robert-Koch-Institut, Berlin, Germany
,
Richard A. Kroczek
2   Molecular Immunology, Robert-Koch-Institut, Berlin, Germany
,
Gert Müller-Berghaus
1   Haemostasis Research Unit, Max-Planck-Institute for Physiological and Clinical Research, Kerckhoff-Klinik GmbH, Bad Nauheim, Germany
› Author Affiliations
Further Information

Publication History

Received 11 May 1998

Accepted after resubmission 28 August 1998

Publication Date:
07 December 2017 (online)

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Summary

CD40 is a type I member of the tumour necrosis factor (TNF) receptor superfamily of proteins, and is present on a wide variety of cells including vascular endothelial cells. Ligation of this receptor on endothelial cells is known to increase expression of inflammatory adhesion molecules. We have recently demonstrated that platelets express the ligand of CD40 (CD154) within seconds of exposure to agonist, and interact with endothelial cells to participate directly in the induction of an inflammatory response. Here we show that activated platelets induce tissue factor (TF) expression on endothelial cells in a CD40/CD154-dependent manner, and that the magnitude of this response can equal that induced by TNFα. Moreover, CD40 ligation on endothelial cells downregulates the expression of thrombomodulin. We also show that CD40-mediated TF expression is less sensitive to inhibition with the oxidative radical scavenger pyrrolidine dithiocarbamate than is that mediated by TNFα, indicating that CD40 has a distinct signalling pathway. Tissue factor is a cell membrane protein which functions as the main trigger of the extrinsic pathway of blood coagulation, and its expression on endothelial cells is implicated in wound healing and angiogenesis. Since platelets are among the first cells involved in haemostasis following tissue injury, our data showing that ligation of CD40 by CD154 induces a procoagulant phenotype on vascular endothelial cells suggests that platelets may play an important role in the induction of wound healing.

 

  • References

  • 1 Stout RD, Suttles J. The many roles of CD40 in cell-mediated inflammatory responses. Immunol. Today 1996; 17: 487-92.
    PubMedGoogle Scholar
  • 2 Gordon J, Millsum JM, Guy GR, Ledbetter JA. Synergistic interaction between interleukin 4 and anti-Bp50 (CDw40) revealed in a novel B cell restimulation assay. Eur J Immunol 1987; 17: 1535-40.
    CrossrefPubMedGoogle Scholar
  • 3 Rathmell JC, Townsend SE, Xu JC, Flavell RA, Goodnow CC. Expansion and elimination of B cells in vivo: Dual roles for CD40- and Fas (CD95)-ligands modulated by the B cell antigen receptor. Cell 1996; 87: 319-29.
    CrossrefPubMedGoogle Scholar
  • 4 Axcrona K, Gray D, Leanderson T. Regulation of B cell growth and differentiation via CD21 and CD40. Eur J Immunol 1996; 26: 2203-7.
    CrossrefPubMedGoogle Scholar
  • 5 Koopman G, Keehnen RMJ, Lindhout E, Zhou DFH, de Groot C, Pals ST. Germinal center B cells rescued from apoptosis by CD40 ligation or attachment to follicular dendritic cells, but not by engagement of surface immunoglobulin or adhesion receptors, become resistant to CD95-induced apoptosis. Eur J Immunol 1997; 27: 1-7.
    CrossrefPubMedGoogle Scholar
  • 6 Hollenbaugh D, Mischel-Petty N, Edwards CP, Simon JC, Denfield RW, Kiener PA, Aruffo A. Expression of functional CD40 by vascular endothelial cells. J Exp Med 1995; 182: 33-40.
    CrossrefPubMedGoogle Scholar
  • 7 Karmann K, Huges CCW, Schechner J, Fanslow WC, Pober JS. CD40 on human endothelial cells: Inducibility by cytokines and functional regulation of adhesion molecule expression. Proc Natl Acad Sci USA 1995; 92: 4342-6.
    CrossrefPubMedGoogle Scholar
  • 8 Yellin MJ, Brett J, Baum D, Matsushima A, Szabolcs M, Stern D, Chess L. Functional interactions of T cells with endothelial cells: The role of CD40L-CD40-mediated signals. J Exp Med 1995; 182: 1857-64.
    CrossrefPubMedGoogle Scholar
  • 9 Karmann K, Min W, Fanslow WC, Pober JS. Activation and homologous desensitization of human endothelial cells by CD40 ligand, tumour necrosis factor, and interleukin 1. J Exp Med 1996; 184: 173-82.
    CrossrefPubMedGoogle Scholar
  • 10 Henn V, Slupsky JR, Gräfe M, Anagnostopolous I, Förster R, Müller-Berghaus G, Kroczek RA. CD40 ligand (CD154) on activated platelets triggers a pro-inflammatory reaction of endothelial cells. Nature 1998; 391: 591-4.
    CrossrefPubMedGoogle Scholar
  • 11 Stern DM, Bank L, Nawroth PP, Cassimeris J, Kisiel W, Fenton JW, Dinarello C, Chess L, Jaffe EA. Self-regulation of procoagulant events on the endothelial cell surface. J Exp Med 1985; 162: 1223-35.
    CrossrefPubMedGoogle Scholar
  • 12 Nawroth P, Stern D. Modulation of endothelial cell hemostatic properties by tumor necrosis factor. J Exp Med 1986; 164: 740-52.
    PubMedGoogle Scholar
  • 13 Moore KL, Andreoli SP, Esmon NL, Esmon CT, Berg NU. Endotoxin enhances tissue factor and suppresses thrombomodulin expression of human vascular endothelium in vitro. J Clin Invest 1987; 79: 124-30.
    CrossrefPubMedGoogle Scholar
  • 14 Mantovani A, Sozzani S, Vecchi A, Introna M, Allavena P. Cytokine activation of endothelial cells: new molecules for an old paradigm. Thromb Haemost 1997; 78: 406-12.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Ruf W, Edgington TS. Structural biology of tissue factor, the initiator of thrombogenesis in vivo. FASEB J 1994; 8: 385-90.
    CrossrefPubMedGoogle Scholar
  • 16 Drake TA, Morrissey JH, Edgington TS. Selective cellular expression of tissue factor in human tissues – Implications for disorders of haemostasis and thrombosis. Am J Pathol 1989; 134: 1087-90.
    PubMedGoogle Scholar
  • 17 Graf D, Müller S, Korthäer U, van Kooten C, Weise C, Kroczek RA. A soluble form of TRAP (CD40 ligand) is rapidly released after T cell activation. Eur J Immunol 1995; 25: 1749-54.
    CrossrefPubMedGoogle Scholar
  • 18 Slupsky JR, Kamiguti AS, Rhodes NP, Cawley JC, Shaw ARE, Zuzel M. The platelet antigens CD9, CD42, and intergrin αIIbβIIIa can be topographically associated and transduce functionally similar signals. Eur J Biochem 1997; 244: 168-75.
    CrossrefPubMedGoogle Scholar
  • 19 Jaffe EA. Culture and identification of large vessel endothelial cells. In: Biology of endothelial cells. Jaffe EA, ed. Boston: Martinus Nijhoff; 1984: 1-13.
    Google Scholar
  • 20 Pötzsch B, Grulich-Henn J, Rössing R, Wille D, Müller-Berhaus G. Identification of endothelial and mesothelial cells in human omental tissue and in omentum-derived cells by specific cell markers. Lab Invest 1990; 52: 2745-56.
    PubMedGoogle Scholar
  • 21 Marui N, Offermann MK, Swerlick R, Kunsch C, Rosen CA, Ahmed M, Alexander RW, Medford RM. Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells. J Clin Invest 1993; 92: 1866-74.
    CrossrefPubMedGoogle Scholar
  • 22 Moll T, Czyz M, Holzmüller H, Hofer-Warbinek R, Wagner E, Winkler H, Bach FH, Hofer E. Regulation of the tissue factor promoter in endothelial cells. Binding of NF-κB, AP-1, and Sp1-like transcription factors. J Biol Chem 1995; 270: 3849-57.
    CrossrefPubMedGoogle Scholar
  • 23 Munoz C, Pascual-Salcedo D, Castellanos MdC, Alfranca A, Aragonés J, Vara A, Redondo JM, de Landázuri MO. Pyrrolidine dithiocarbamate inhibits the production of interleukin 6, interleukin 8, and granulocyte-macrophage colony-stimulating factor by human endothelial cells in response to inflammatory mediators: Modulation of NF-kB and AP-1 transcription factors activity. Blood 1996; 88: 3482-90.
    PubMedGoogle Scholar
  • 24 Orthner CL, Rodgers GM, Fitzgerald LA. Pyrrolidine dithiocarbamate abrogates tissue factor (TF) expression by endothelial cells: Evidence implicating nuclear factor-κB in TF induction by diverse agents. Blood 1995; 86: 436-43.
    PubMedGoogle Scholar
  • 25 Davie EW. Biochemical and molecular aspects of the coagulation cascade. Thromb Haemost 1995; 74: 1-6.
    PubMedGoogle Scholar
  • 26 Liu Z, Hsu H, Goeddel DV, Karin M. Dissection of TNF receptor 1 effector funtions: JNK activation is not linked to apoptosis while NF-κB activation prevents cell death. Cell 1996; 87: 565-76.
    CrossrefPubMedGoogle Scholar
  • 27 Gawaz M, Neumann FJ, Ott I, Schiessler A, Schömig A. Platelet function in acute myocardial infarction treated with direct angioplasty. Circulation 1996; 93: 229-37.
    CrossrefPubMedGoogle Scholar
  • 28 Zahger D, Fishbein MC, Garfinkel LI, Shah PK, Forrester JS, Regnstrom J, Yano J, Cercek B. VCL, an antagonist of the platelet gpIb receptor, markedly inhibits platelet adhesion and intimal thickening after balloon injury in the rat. Circulation 1995; 92: 1269-73.
    CrossrefPubMedGoogle Scholar
  • 29 Contrino J, Hair G, Kreutzer DL, Rickles FR. In situ detection of tissue factor in vascular endothelial cells: correlation with the malignant phenotype of human breast disease. Nature (Medicine) 1996; 2: 209-15.
    PubMedGoogle Scholar
  • 30 Cines DB, Pollak ES, Buck CA, Loscalzo J, Zimmerman GA, McEver RP, Pober JS, Wick TM, Konkle BA, Schwartz BS, Barnathan ES, McCrae KR, Hug BA, Schmidt A-M, Stern DM. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 1998; 91: 3527-61.
    PubMedGoogle Scholar
  • 31 Pradier O, Williams F, Abramowicz DA, Schandené L, de Boer M, Thielemans K, Capel P, Goldman M. CD40 engagement induces monocyte procoagulant activity through and interleukin-10 resistant pathway. Eur J Immunol 1996; 26: 3048-54.
    CrossrefPubMedGoogle Scholar
  • 32 Diacovo TG, Puri KD, Warnock RA, Springer TA, von Andrian UH. Platelet-mediated lymphocyte delivery to high endothelial venules. Science 1996; 273: 252-5.
    CrossrefPubMedGoogle Scholar
  • 33 Diacovo TG, Catalina MD, Siegelman MH, von Andrian UH. Circulating activated platelets reconstitute lymphocyte homing and immunity in L-selectin-deficient mice. J Exp Med 1997; 187: 197-204.
    PubMedGoogle Scholar