Tissue Factor Coagulant Activity is Regulated by the Plasma Membrane Microenvironment

Abstract

Background Tissue factor (TF) can be present in a non-coagulant and coagulant form. Whether the coagulant activity is affected by the plasma membrane microenvironment is unexplored.

Objective This article studies the presence and coagulant activity of human TF in plasma membrane micro-domains.

Methods Plasma membranes were isolated from human MIA PaCa2 cells, MDA-MB-231 cells and human vascular smooth muscle cells by Percoll gradient ultracentrifugation after cell disruption. Plasma membranes were fractionated by OptiPrep gradient ultracentrifugation, and the presence of TF, flotillin, caveolin, clathrin, protein disulphide isomerase (PDI), TF pathway inhibitor (TFPI) and phosphatidylserine (PS) were determined.

Results Plasma membranes contain two detergent-resistant membrane (DRM) compartments differing in density and biochemical composition. High-density DRMs (DRM-H) have a density (ρ) of 1.15 to 1.20 g/mL and contain clathrin, whereas low-density DRMs (DRM-L) have a density between 1.09 and 1.13 g/mL and do not contain clathrin. Both DRMs contain TF, flotillin and caveolin. PDI is detectable in DRM-H, TFPI is not detectable in either DMR-H or DRM-L and PS is detectable in DRM-L. The DRM-H-associated TF (> 95% of the TF antigen) lacks detectable coagulant activity, whereas the DRM-L-associated TF triggers coagulation. This coagulant activity is inhibited by lactadherin and thus PS-dependent, but seemed insensitive to 16F16, an inhibitor of PDI.

Conclusion Non-coagulant and coagulant TF are present within different types of DRMs in the plasma membrane, and the composition of these DRMs may affect the TF coagulant activity.

Keywords

tissue factor - coagulant activity - phosphatidylserine - plasma membrane - detergent-resistant membrane

• References

• 1 Nebl T, Pestonjamasp KN, Leszyk JD, Crowley JL, Oh SW, Luna EJ. Proteomic analysis of a detergent-resistant membrane skeleton from neutrophil plasma membranes. J Biol Chem 2002; 277 (45) 43399-43409
• 2 Bhattacharya J, Peters PJ, Clapham PR. Human immunodeficiency virus type 1 envelope glycoproteins that lack cytoplasmic domain cysteines: impact on association with membrane lipid rafts and incorporation onto budding virus particles. J Virol 2004; 78 (10) 5500-5506
• 3 Fernandes MJ, Rollet-Labelle E, Paré G. , et al. CD16b associates with high-density, detergent-resistant membranes in human neutrophils. Biochem J 2006; 393 (Pt 1): 351-359
• 4 Rollet-Labelle E, Marois S, Barbeau K, Malawista SE, Naccache PH. Recruitment of the cross-linked opsonic receptor CD32A (FcgammaRIIA) to high-density detergent-resistant membrane domains in human neutrophils. Biochem J 2004; 381 (Pt 3): 919-928
• 5 Awasthi V, Mandal SK, Papanna V, Rao LV, Pendurthi UR. Modulation of tissue factor-factor VIIa signaling by lipid rafts and caveolae. Arterioscler Thromb Vasc Biol 2007; 27 (06) 1447-1455
• 6 Del Conde I, Shrimpton CN, Thiagarajan P, López JA. Tissue-factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation. Blood 2005; 106 (05) 1604-1611
• 7 Dietzen DJ, Page KL, Tetzloff TA. Lipid rafts are necessary for tonic inhibition of cellular tissue factor procoagulant activity. Blood 2004; 103 (08) 3038-3044
• 8 Dietzen DJ, Page KL, Tetzloff TA, Bohrer A, Turk J. Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase blunts factor VIIa/tissue factor and prothrombinase activities via effects on membrane phosphatidylserine. Arterioscler Thromb Vasc Biol 2007; 27 (03) 690-696
• 9 Fortin JP, Rivard GE, Adam A, Marceau F. Studies on rabbit natural and recombinant tissue factors: intracellular retention and regulation of surface expression in cultured cells. Am J Physiol Heart Circ Physiol 2005; 288 (05) H2192-H2202
• 10 Henriquez S, Calderon C, Quezada M. , et al. Progesterone utilizes distinct membrane pools of tissue factor to increase coagulation and invasion and these effects are inhibited by TFPI. J Cell Physiol 2011; 226 (12) 3278-3285
• 11 Kato S, Pinto M, Carvajal A. , et al. Tissue factor is regulated by epidermal growth factor in normal and malignant human endometrial epithelial cells. Thromb Haemost 2005; 94 (02) 444-453
• 12 Sevinsky JR, Rao LV, Ruf W. Ligand-induced protease receptor translocation into caveolae: a mechanism for regulating cell surface proteolysis of the tissue factor-dependent coagulation pathway. J Cell Biol 1996; 133 (02) 293-304
• 13 Mandal SK, Pendurthi UR, Rao LV. Cellular localization and trafficking of tissue factor. Blood 2006; 107 (12) 4746-4753
• 14 Dietzen DJ, Jack GG, Page KL, Tetzloff TA, Hall CL, Mast AE. Localization of tissue factor pathway inhibitor to lipid rafts is not required for inhibition of factor VIIa/tissue factor activity. Thromb Haemost 2003; 89 (01) 65-73
• 15 Maroney SA, Ellery PE, Wood JP, Ferrel JP, Bonesho CE, Mast AE. Caveolae optimize tissue factor-Factor VIIa inhibitory activity of cell-surface-associated tissue factor pathway inhibitor. Biochem J 2012; 443 (01) 259-266
• 16 Abid Hussein MN, Meesters EW, Osmanovic N, Romijn FP, Nieuwland R, Sturk A. Antigenic characterization of endothelial cell-derived microparticles and their detection ex vivo. J Thromb Haemost 2003; 1 (11) 2434-2443
• 17 Fauvel J, Chap H, Roques V, Levy-Toledano S, Douste-Blazy L. Biochemical characterization of plasma membranes and intracellular membranes isolated from human platelets using Percoll gradients. Biochim Biophys Acta 1986; 856 (01) 155-164
• 18 Ford T, Graham J, Rickwood D. Iodixanol: a nonionic iso-osmotic centrifugation medium for the formation of self-generated gradients. Anal Biochem 1994; 220 (02) 360-366
• 19 Berckmans RJ, Sturk A, van Tienen LM, Schaap MC, Nieuwland R. Cell-derived vesicles exposing coagulant tissue factor in saliva. Blood 2011; 117 (11) 3172-3180
• 20 Duchemin J, Pan-Petesch B, Arnaud B, Blouch MT, Abgrall JF. Influence of coagulation factors and tissue factor concentration on the thrombin generation test in plasma. Thromb Haemost 2008; 99 (04) 767-773
• 21 Puy C, Tucker EI, Ivanov IS. , et al. Platelet-derived short-chain polyphosphates enhance the inactivation of tissue factor pathway inhibitor by activated coagulation factor XI. PLoS One 2016; 11 (10) e0165172
• 22 Broquet AH, Thomas G, Masliah J, Trugnan G, Bachelet M. Expression of the molecular chaperone Hsp70 in detergent-resistant microdomains correlates with its membrane delivery and release. J Biol Chem 2003; 278 (24) 21601-21606
• 23 Furlan-Freguia C, Marchese P, Gruber A, Ruggeri ZM, Ruf W. P2 × 7 receptor signaling contributes to tissue factor-dependent thrombosis in mice. J Clin Invest 2011; 121 (07) 2932-2944
• 24 Krudysz-Amblo J, Jennings II ME, Knight T, Matthews DE, Mann KG, Butenas S. Disulfide reduction abolishes tissue factor cofactor function. Biochim Biophys Acta 2013; 1830 (06) 3489-3496
• 25 Chen VM, Ahamed J, Versteeg HH, Berndt MC, Ruf W, Hogg PJ. Evidence for activation of tissue factor by an allosteric disulfide bond. Biochemistry 2006; 45 (39) 12020-12028
• 26 Neuenschwander PF, Bianco-Fisher E, Rezaie AR, Morrissey JH. Phosphatidylethanolamine augments factor VIIa-tissue factor activity: enhancement of sensitivity to phosphatidylserine. Biochemistry 1995; 34 (43) 13988-13993
• 27 Wolberg AS, Monroe DM, Roberts HR, Hoffman MR. Tissue factor de-encryption: ionophore treatment induces changes in tissue factor activity by phosphatidylserine-dependent and -independent mechanisms. Blood Coagul Fibrinolysis 1999; 10 (04) 201-210
• 28 Langer F, Ruf W. Synergies of phosphatidylserine and protein disulfide isomerase in tissue factor activation. Thromb Haemost 2014; 111 (04) 590-597
• 29 Le DT, Rapaport SI, Rao LV. Studies of the mechanism for enhanced cell surface factor VIIa/tissue factor activation of factor X on fibroblast monolayers after their exposure to N-ethylmaleimide. Thromb Haemost 1994; 72 (06) 848-855
• 30 Sen P, Neuenschwander PF, Pendurthi UR, Rao LV. Analysis of factor VIIa binding to relipidated tissue factor by surface plasmon resonance. Blood Coagul Fibrinolysis 2010; 21 (04) 376-379
• 31 Shaw AW, Pureza VS, Sligar SG, Morrissey JH. The local phospholipid environment modulates the activation of blood clotting. J Biol Chem 2007; 282 (09) 6556-6563
• 32 Ansari SA, Pendurthi UR, Sen P, Rao LV. The role of putative phosphatidylserine-interactive residues of tissue factor on its coagulant activity at the cell surface. PLoS One 2016; 11 (06) e0158377
• 33 Ke K, Yuan J, Morrissey JH. Tissue factor residues that putatively interact with membrane phospholipids. PLoS One 2014; 9 (02) e88675
• 34 Babiychuk EB, Draeger A. Biochemical characterization of detergent-resistant membranes: a systematic approach. Biochem J 2006; 397 (03) 407-416
• 35 Hölschermann H, Hilgendorff A, Kemkes-Matthes B. , et al. Simvastatin attenuates vascular hypercoagulability in cardiac transplant recipients. Transplantation 2000; 69 (09) 1830-1836
• 36 Tripodi A, Pellegatta F, Chantarangkul V. , et al. Statins decrease thrombin generation in patients with hypercholesterolemia. Eur J Intern Med 2014; 25 (05) 449-451
• 37 Nordøy A, Svensson B, Hansen JB. Atorvastatin and omega-3 fatty acids protect against activation of the coagulation system in patients with combined hyperlipemia. J Thromb Haemost 2003; 1 (04) 690-697