Factor VIIa Induced Release of von Willebrand Factor from Human Umbilical Vein Endothelial Cells by a Tyrosine Kinase Dependent Pathway

Simon A. Brown; Derrick J. Bowen; Maurice B. Hallett; John C. Giddings; Peter W. Collins

doi:10.1055/s-0037-1613132

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2002; 87(06): 1057-1061
DOI: 10.1055/s-0037-1613132

Review Article

Schattauer GmbH

Factor VIIa Induced Release of von Willebrand Factor from Human Umbilical Vein Endothelial Cells by a Tyrosine Kinase Dependent Pathway

Authors

Simon A. Brown

¹Departments of Haematology & Surgery, University of Wales College of Medicine, Cardiff, Wales, UK
Derrick J. Bowen

¹Departments of Haematology & Surgery, University of Wales College of Medicine, Cardiff, Wales, UK
Maurice B. Hallett

¹Departments of Haematology & Surgery, University of Wales College of Medicine, Cardiff, Wales, UK
John C. Giddings

¹Departments of Haematology & Surgery, University of Wales College of Medicine, Cardiff, Wales, UK
Peter W. Collins

¹Departments of Haematology & Surgery, University of Wales College of Medicine, Cardiff, Wales, UK

Abstract

Summary

The interaction of FVIIa with surface-bound tissue factor (TF) induces various cellular changes including cytosolic Ca²⁺ signals. The release of von Willebrand factor (VWF) from endothelial cell stores may be triggered by an elevation in cytosolic free Ca²⁺, therefore we investigated the effect of rFVIIa on the release of VWF from human umbilical vein endothelial cells (HUVEC). We show here that rFVIIa induces the release of VWF from HUVEC with or without prestimulation with lipopolysaccharide (LPS). The effect of rFVIIa was dose dependent. However, the release of VWF by HUVEC in response to rFVIIa was significantly greater with LPS prestimulation (3.18 times control) than without LPS prestimulation (1.45 times control) (p <0.001). Cytosolic Ca²⁺ signals were detectable only after LPS prestimulation of HUVEC and these were small compared to those elicited by thrombin. No effect on rFVIIa induced release of VWF was seen in the presence of hirudin, site inactivated rFVIIa or the protein kinase C (PKC) inhibitor staurosporine. However, a tyrosine kinase inhibitor genistein, inhibited the rFVIIa induced release of VWF. These data show that release of VWF can occur without involvement of the cytosolic Ca²⁺/ PKC pathway. FVIIa induced VWF release from endothelial cells may have in vivo significance at sites of TF expression.

Keywords

Factor VIIa - von Willebrand factor - tyrosine kinase - human umbilical vein endothelium - calcium flux

Full Text

References

References
1 Mann KG. Biochemistry and physiology of blood coagulation. Thromb Haemost 1999; 82: 165-74.
2 Bazan JF. Structural design and molecular evolution of a cytokine receptor superfamily. Proc Natl Sci USA 1990; 87: 6934-8.
3 Rottingen JA, Enden T, Camerer E, Iversen JG, Prydz H. Binding of human factor VIIa to tissue factor induces cytosolic Ca²⁺ signals in J82 cells, transfected COS-1 cells, Mardin-Darby Canine Kidney Cells and in Human Endothelial cells induced to synthesize tissue factor. J Biol Chem 1995; 270: 4650-60.
4 Pendurthi UR, Alok D, Rao LVM. Binding of factor VIIa to tissue factor induces alterations in gene expression in human fibroblast cells: up-regulation of poly(A) polymerase. Proc Natl Acad Sci USA 1997; 94: 12598-603.
5 Taniguchi T, Kakkar AK, Tuddenham EGD, Williamson RCN, Lemoine NR. Enhanced expression or urokinase receptor induced through the tissue factor-factor VIIa pathway in human pancreatic cancer. Cancer Res 1998; 58: 4461-7.
6 Ollivier V, Bentolila S, Chabbat J, Hakim J, de Prost D. Tissue factor-dependent vascular endothelial growth factor production by human fibroblasts in response to activated factor VII. Blood 1998; 91: 2698-703.
7 Masuda M, Nakamura S, Murakami T, Komiyama Y, Takahashi H. Association of tissue factor with a γ chain homodimer of the IgE receptor type 1 in cultured human monocytes. Eur J Immunol 1996; 26: 2529-32.
8 Birch KA, Pober JS, Zavoico GB, Means AR, Ewenstein BM. Calcium/calmodulin transduces thrombin-stimulated secretion: studies in intact and minimally permeabilized human umbilical vein endothelial cells. J Cell Biol 1992; 118: 1501-10.
9 Jaffe EA, Nachman RL, Becker CG, Minick CR. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest 1973; 52: 2745-56.
10 Collins PW, Noble KE, Reittie JR, Hoffbrand AV, Pasi KJ, Yong KL. Induction of tissue factor expression in human monocyte/endothelium cocultures. Br J Haematol 1995; 91: 963-70.
11 Wheeler-Jones CPD, May MJ, Morgan AJ, Pearson JD. Protein tyrosine kinases regulate agonist-stimulated prostacyclin release but not von Willebrand factor secretion from human umbilical vein endothelial cells. Bioch J 1996; 315: 407-16.
12 Short PE, Williams CE, Picken AM, Hill FG. Factor VIII related antigen: an improved enzyme immunoassay. Med Lab Sci 1982; 39: 351-5.
13 Hallett MB, Davies EV, Pettit EJ. Fluorescent methods for measuring and imaging the cytosolic free Ca²⁺ in neutrophils. Methods 1996; 09: 591-606.
14 Wiiger MT, Pringle S, Pettersen KS, Narahara N, Prydz H. Effects of binding of ligand (FVIIa) to induced tissue factor in human endothelial cells. Thromb Res 2000; 98: 311-21.
15 Reuning U, Preissner KT, Muller-Berghaus G. Two independent binding sites on monolayers of human endothelial cells are responsible for interaction with coagulation factor VII and factor VIIa. Thromb Haemost 1993; 69: 197-204.
16 Camerer E, Røttingen JA, Iversen JG, Prydz H. Coagulation factors VII and X induce Ca²⁺ oscillations in Madin-Darby Canine Kidney cells only when proteolytically active. J Biol Chem 1996; 271: 29034-42.
17 Camerer E, Røttingen JA, Gjernes E, Larsen K, Skartlien AH, Iversen JG, Prydz H. Coagulation factors VIIa and Xa induce cell signaling leading to up-regulation of egr-1 gene. J Biol Chem 1999; 274: 32225-33.
18 Sorensen BB, Freskgard P-O, Nielsen LS, Rao LVM, Ezban M, Petersen LC. Factor VIIa-induced p44/42 Mitogen-activated protein kinase activation requires the proteolytic activity of Factor VIIa and is independent of the tissue factor cytoplasmic domain. J Biol Chem 1999; 274: 21349-54.
19 Cunningham MA, Romas P, Hutchinson P, Holdsworth SR, Tipping PG. Tissue factor and factor VIIa receptor/ligand interactions induce proinflammatory effects in macrophages. Blood 1999; 94: 3413-20.
20 Cambier JC. Antigen and Fc receptor signalling. The awesome power of the immunoreceptor tyrosine-based activation motif (ITAM). J Immunol 1995; 155: 3281-5.
21 Carew MA, Paleolog EM, Pearson JD. The roles of protein kinase C and intracellular Ca²⁺ in the secretion of von Willebrand factor from human vascular endothelial cells. Biochem J 1995; 286: 631-5.
22 Loesberg C, Gonsalves MD, Zandbergen J, Willems C, van Aken WG, Stel HV, van Mourik JA, De Groot PG. The effect of calcium on the secretion of factor VIII-related antigen by cultured human endothelial cells. Biochim Biophys Acta 1983; 763: 150-68.
23 Vischer UM, Wollheim CB. Epinephrine induces von Willebrand factor release from cultured endothelial cells: involvement of cyclic AMPdependent signaling in exocytosis. Thromb Haemost 1997; 77: 1182-8.
24 Vischer UM, Wollheim CB. Purine nucleotides induce regulated secretion of von Willebrand factor: involvement of cytosolic Ca²⁺ and cyclic adenosine monophosphate-dependent signaling in endothelial exocytosis. Blood 1998; 91: 118-27.
25 Fayos BE, Wattenberg BW. Regulated exocytosis in vascular endothelial cells can be triggered by intracellular guanine nucleotides and requires a hydrophobic, thiol-sensitive component. Studies of regulated von Willebrand factor secretion from digitonin permeabilized endothelial cells. Endothelium 1997; 05: 339-50.
26 de Leeuw HPJC, Wijers-Koster PM, van Mourik JA, Voorberg J. Small GTP-binding protein RalA associates with Weibel-Palade bodies in endothelial cells. Thromb Haemost 1999; 82: 1177-81.
27 Berridge MJ. Inositol triphosphate and calcium signalling. Nature 1993; 361: 315-25.