Download PDF
Semin Thromb Hemost 2017; 43(2): 129-134
DOI: 10.1055/s-0036-1592301
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Microparticles and Fibrinolysis

Loris Vallier
1   VRCM, UMR_S1076, UFR de Pharmacie, Aix-Marseille Université, INSERM, Marseille, France
,
Sylvie Cointe
1   VRCM, UMR_S1076, UFR de Pharmacie, Aix-Marseille Université, INSERM, Marseille, France
2   Department of Hematology and Vascular Biology, CHU La Conception, APHM, Marseille, France
,
Romaric Lacroix
1   VRCM, UMR_S1076, UFR de Pharmacie, Aix-Marseille Université, INSERM, Marseille, France
2   Department of Hematology and Vascular Biology, CHU La Conception, APHM, Marseille, France
,
Amandine Bonifay
1   VRCM, UMR_S1076, UFR de Pharmacie, Aix-Marseille Université, INSERM, Marseille, France
,
Coralie Judicone
2   Department of Hematology and Vascular Biology, CHU La Conception, APHM, Marseille, France
,
Françoise Dignat-George
1   VRCM, UMR_S1076, UFR de Pharmacie, Aix-Marseille Université, INSERM, Marseille, France
2   Department of Hematology and Vascular Biology, CHU La Conception, APHM, Marseille, France
,
Hau C. Kwaan
3   Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
› Author Affiliations
Further Information

Publication History

Publication Date:
06 December 2016 (online)

    Permissions and Reprints

Abstract

Microparticles (MPs) are submicronic vesicles which are formed by budding of the cellular membrane of virtually any cell type in response to cell activation or apoptosis. Both circulating MPs and MPs generated within tissues harbor molecules with a large repertoire of biological activities and transfer material to target cells. Depending on their cellular origin, the stimuli triggering their formation, or their localization, they may participate in the maintenance of organ or vascular homeostasis as well as inducing dysfunction. MPs have mostly been described as having procoagulant properties. However, the fact that some MP subsets are able to efficiently generate plasmin suggests that the role of MPs in hemostasis is more complex than initially thought. In this review, we summarize key findings showing that MPs provide a heterogeneous catalytic surface for plasmin generation, according to their cellular origin. We further address the specific features of the MP-dependent fibrinolytic system. Potential consequences of this MP-associated fibrinolytic activity in pathology are illustrated in cancer.

Keywords

extracellular vesicles - cancer - fibrinolysis - hemostasis - microparticles
 

  • References

  • 1 Akers JC, Gonda D, Kim R, Carter BS, Chen CC. Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J Neurooncol 2013; 113 (1) 1-11
    CrossrefPubMedGoogle Scholar
  • 2 Piccin A, Murphy WG, Smith OP. Circulating microparticles: pathophysiology and clinical implications. Blood Rev 2007; 21 (3) 157-171
    CrossrefPubMedGoogle Scholar
  • 3 Zwicker JI. Tissue factor-bearing microparticles and cancer. Semin Thromb Hemost 2008; 34 (2) 195-198
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Théry C, Ostrowski M, Segura E. Membrane vesicles as conveyors of immune responses. Nat Rev Immunol 2009; 9 (8) 581-593
    CrossrefPubMedGoogle Scholar
  • 5 De Toro J, Herschlik L, Waldner C, Mongini C. Emerging roles of exosomes in normal and pathological conditions: new insights for diagnosis and therapeutic applications. Front Immunol 2015; 6: 203
    PubMedGoogle Scholar
  • 6 Ihara T, Yamamoto T, Sugamata M, Okumura H, Ueno Y. The process of ultrastructural changes from nuclei to apoptotic body. Virchows Arch 1998; 433 (5) 443-447
    CrossrefPubMedGoogle Scholar
  • 7 Taylor RC, Cullen SP, Martin SJ. Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol 2008; 9 (3) 231-241
    CrossrefPubMedGoogle Scholar
  • 8 Chou J, Mackman N, Merrill-Skoloff G, Pedersen B, Furie BC, Furie B. Hematopoietic cell-derived microparticle tissue factor contributes to fibrin formation during thrombus propagation. Blood 2004; 104 (10) 3190-3197
    CrossrefPubMedGoogle Scholar
  • 9 Camussi G, Deregibus MC, Bruno S, Cantaluppi V, Biancone L. Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney Int 2010; 78 (9) 838-848
    CrossrefPubMedGoogle Scholar
  • 10 Owens III AP, Mackman N. Microparticles in hemostasis and thrombosis. Circ Res 2011; 108 (10) 1284-1297
    CrossrefPubMedGoogle Scholar
  • 11 Agouti I, Cointe S, Robert S , et al. Platelet and not erythrocyte microparticles are procoagulant in transfused thalassaemia major patients. Br J Haematol 2015; 171 (4) 615-624
    CrossrefPubMedGoogle Scholar
  • 12 Zarfati M, Katz T, Avivi I, Brenner B, Aharon A. PO-45 - The role of microvesicles in multiple myeloma progression. Thromb Res 2016; 140 (Suppl. 01) S193
    PubMedGoogle Scholar
  • 13 Mezouar S, Darbousset R, Dignat-George F, Panicot-Dubois L, Dubois C. Inhibition of platelet activation prevents the P-selectin and integrin-dependent accumulation of cancer cell microparticles and reduces tumor growth and metastasis in vivo. Int J Cancer 2015; 136 (2) 462-475
    CrossrefPubMedGoogle Scholar
  • 14 Lwaleed BA, Lam L, Lasebai M, Cooper AJ. Expression of tissue factor and tissue factor pathway inhibitor in microparticles and subcellular fractions of normal and malignant prostate cell lines. Blood Coagul Fibrinolysis 2013; 24 (3) 339-343
    CrossrefPubMedGoogle Scholar
  • 15 Kushak RI, Nestoridi E, Lambert J, Selig MK, Ingelfinger JR, Grabowski EF. Detached endothelial cells and microparticles as sources of tissue factor activity. Thromb Res 2005; 116 (5) 409-419
    CrossrefPubMedGoogle Scholar
  • 16 Maroney SA, Haberichter SL, Friese P , et al. Active tissue factor pathway inhibitor is expressed on the surface of coated platelets. Blood 2007; 109 (5) 1931-1937
    CrossrefPubMedGoogle Scholar
  • 17 Keuren JFW, Magdeleyns EJ, Govers-Riemslag JW, Lindhout T, Curvers J. Effects of storage-induced platelet microparticles on the initiation and propagation phase of blood coagulation. Br J Haematol 2006; 134 (3) 307-313
    CrossrefPubMedGoogle Scholar
  • 18 Brisset A-C, Terrisse A-D, Dupouy D , et al. Shedding of active tissue factor by aortic smooth muscle cells (SMCs) undergoing apoptosis. Thromb Haemost 2003; 90 (3) 511-518
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Aharon A, Tamari T, Brenner B. Monocyte-derived microparticles and exosomes induce procoagulant and apoptotic effects on endothelial cells. Thromb Haemost 2008; 100 (5) 878-885
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Angelillo-Scherrer A. Leukocyte-derived microparticles in vascular homeostasis. Circ Res 2012; 110 (2) 356-369
    CrossrefPubMedGoogle Scholar
  • 21 Koshiar RL, Somajo S, Norström E, Dahlbäck B. Erythrocyte-derived microparticles supporting activated protein C-mediated regulation of blood coagulation. PLoS ONE 2014; 9 (8) e104200
    CrossrefPubMedGoogle Scholar
  • 22 Lacroix R, Sabatier F, Mialhe A , et al. Activation of plasminogen into plasmin at the surface of endothelial microparticles: a mechanism that modulates angiogenic properties of endothelial progenitor cells in vitro. Blood 2007; 110 (7) 2432-2439
    CrossrefPubMedGoogle Scholar
  • 23 Ginestra A, Monea S, Seghezzi G , et al. Urokinase plasminogen activator and gelatinases are associated with membrane vesicles shed by human HT1080 fibrosarcoma cells. J Biol Chem 1997; 272 (27) 17216-17222
    CrossrefPubMedGoogle Scholar
  • 24 Ginestra A, La Placa MD, Saladino F, Cassarà D, Nagase H, Vittorelli ML. The amount and proteolytic content of vesicles shed by human cancer cell lines correlates with their in vitro invasiveness. Anticancer Res 1998; 18 (5A): 3433-3437
    PubMedGoogle Scholar
  • 25 Ginestra A, Miceli D, Dolo V, Romano FM, Vittorelli ML. Membrane vesicles in ovarian cancer fluids: a new potential marker. Anticancer Res 1999; 19 (4C): 3439-3445
    PubMedGoogle Scholar
  • 26 Dolo V, Ginestra A, Cassarà D , et al. Selective localization of matrix metalloproteinase 9, beta1 integrins, and human lymphocyte antigen class I molecules on membrane vesicles shed by 8701-BC breast carcinoma cells. Cancer Res 1998; 58 (19) 4468-4474
    PubMedGoogle Scholar
  • 27 Dolo V, D'Ascenzo S, Violini S , et al. Matrix-degrading proteinases are shed in membrane vesicles by ovarian cancer cells in vivo and in vitro. Clin Exp Metastasis 1999; 17 (2) 131-140
    CrossrefPubMedGoogle Scholar
  • 28 Angelucci A, D'Ascenzo S, Festuccia C , et al. Vesicle-associated urokinase plasminogen activator promotes invasion in prostate cancer cell lines. Clin Exp Metastasis 2000; 18 (2) 163-170
    CrossrefPubMedGoogle Scholar
  • 29 Graves LE, Ariztia EV, Navari JR, Matzel HJ, Stack MS, Fishman DA. Proinvasive properties of ovarian cancer ascites-derived membrane vesicles. Cancer Res 2004; 64 (19) 7045-7049
    CrossrefPubMedGoogle Scholar
  • 30 Lacroix R, Plawinski L, Robert S , et al. Leukocyte- and endothelial-derived microparticles: a circulating source for fibrinolysis. Haematologica 2012; 97 (12) 1864-1872
    CrossrefPubMedGoogle Scholar
  • 31 Lacroix R, Dignat-George F. Microparticles: new protagonists in pericellular and intravascular proteolysis. Semin Thromb Hemost 2013; 39 (1) 33-39
    Article in Thieme ConnectPubMedGoogle Scholar
  • 32 Dejouvencel T, Doeuvre L, Lacroix R , et al. Fibrinolytic cross-talk: a new mechanism for plasmin formation. Blood 2010; 115 (10) 2048-2056
    CrossrefPubMedGoogle Scholar
  • 33 Lijnen HR. Elements of the fibrinolytic system. Ann N Y Acad Sci 2001; 936: 226-236
    CrossrefPubMedGoogle Scholar
  • 34 Falati S, Liu Q, Gross P , et al. Accumulation of tissue factor into developing thrombi in vivo is dependent upon microparticle P-selectin glycoprotein ligand 1 and platelet P-selectin. J Exp Med 2003; 197 (11) 1585-1598
    CrossrefPubMedGoogle Scholar
  • 35 Thomas GM, Panicot-Dubois L, Lacroix R, Dignat-George F, Lombardo D, Dubois C. Cancer cell-derived microparticles bearing P-selectin glycoprotein ligand 1 accelerate thrombus formation in vivo. J Exp Med 2009; 206 (9) 1913-1927
    CrossrefPubMedGoogle Scholar
  • 36 Khorana AA, Connolly GC. Assessing risk of venous thromboembolism in the patient with cancer. J Clin Oncol 2009; 27 (29) 4839-4847
    CrossrefPubMedGoogle Scholar
  • 37 Khorana AA, Dalal M, Lin J, Connolly GC. Incidence and predictors of venous thromboembolism (VTE) among ambulatory high-risk cancer patients undergoing chemotherapy in the United States. Cancer 2013; 119 (3) 648-655
    CrossrefPubMedGoogle Scholar
  • 38 Nomura S, Niki M, Nisizawa T, Tamaki T, Shimizu M. Microparticles as Biomarkers of Blood Coagulation in Cancer. Biomark Cancer 2015; 7: 51-56
    PubMedGoogle Scholar
  • 39 van Es N, Bleker S, Sturk A, Nieuwland R. Clinical significance of tissue factor-exposing microparticles in arterial and venous thrombosis. Semin Thromb Hemost 2015; 41 (7) 718-727
    Article in Thieme ConnectPubMedGoogle Scholar
  • 40 Thomas GM, Brill A, Mezouar S , et al. Tissue factor expressed by circulating cancer cell-derived microparticles drastically increases the incidence of deep vein thrombosis in mice. J Thromb Haemost 2015; 13 (7) 1310-1319
    CrossrefPubMedGoogle Scholar
  • 41 Zwicker JI. Predictive value of tissue factor bearing microparticles in cancer associated thrombosis. Thromb Res 2010; 125 (Suppl. 02) S89-S91
    CrossrefPubMedGoogle Scholar
  • 42 Jung T, Castellana D, Klingbeil P , et al. CD44v6 dependence of premetastatic niche preparation by exosomes. Neoplasia 2009; 11 (10) 1093-1105
    CrossrefPubMedGoogle Scholar
  • 43 Lo-Coco F, Ammatuna E. The biology of acute promyelocytic leukemia and its impact on diagnosis and treatment. Hematology (Am Soc Hematol Educ Program) 2006; •••: 156-161, 514
    PubMedGoogle Scholar
  • 44 Melnick A, Licht JD. Deconstructing a disease: RARalpha, its fusion partners, and their roles in the pathogenesis of acute promyelocytic leukemia. Blood 1999; 93 (10) 3167-3215
    CrossrefPubMedGoogle Scholar
  • 45 Wang Z-Y, Chen Z. Acute promyelocytic leukemia: from highly fatal to highly curable. Blood 2008; 111 (5) 2505-2515
    CrossrefPubMedGoogle Scholar
  • 46 de la Serna J, Montesinos P, Vellenga E , et al. Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and idarubicin. Blood 2008; 111 (7) 3395-3402
    CrossrefPubMedGoogle Scholar
  • 47 Lehmann S, Ravn A, Carlsson L , et al. Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry. Leukemia 2011; 25 (7) 1128-1134
    CrossrefPubMedGoogle Scholar
  • 48 Myers TJ, Rickles FR, Barb C, Cronlund M. Fibrinopeptide A in acute leukemia: relationship of activation of blood coagulation to disease activity. Blood 1981; 57 (3) 518-525
    CrossrefPubMedGoogle Scholar
  • 49 Bauer KA, Rosenberg RD. Thrombin generation in acute promyelocytic leukemia. Blood 1984; 64 (4) 791-796
    CrossrefPubMedGoogle Scholar
  • 50 Tallman MS, Lefèbvre P, Baine RM , et al. Effects of all-trans retinoic acid or chemotherapy on the molecular regulation of systemic blood coagulation and fibrinolysis in patients with acute promyelocytic leukemia. J Thromb Haemost 2004; 2 (8) 1341-1350
    CrossrefPubMedGoogle Scholar
  • 51 Wang J, Weiss I, Svoboda K, Kwaan HC. Thrombogenic of cell undergoing apoptosis. Brit J Haematol 2001; 115: 382-391
    CrossrefPubMedGoogle Scholar
  • 52 Bennett B, Booth NA, Croll A, Dawson AA. The bleeding disorder in acute promyelocytic leukaemia: fibrinolysis due to u-PA rather than defibrination. Br J Haematol 1989; 71 (4) 511-517
    CrossrefPubMedGoogle Scholar
  • 53 Tapiovaara H, Matikainen S, Hurme M, Vaheri A. Induction of differentiation of promyelocytic NB4 cells by retinoic acid is associated with rapid increase in urokinase activity subsequently downregulated by production of inhibitors. Blood 1994; 83 (7) 1883-1891
    CrossrefPubMedGoogle Scholar
  • 54 Tapiovaara H, Alitalo R, Stephens R, Myöhänen H, Ruutu T, Vaheri A. Abundant urokinase activity on the surface of mononuclear cells from blood and bone marrow of acute leukemia patients. Blood 1993; 82 (3) 914-919
    CrossrefPubMedGoogle Scholar
  • 55 Stephens R, Alitalo R, Tapiovaara H, Vaheri A. Production of an active urokinase by leukemia cells: a novel distinction from cell lines of solid tumors. Leuk Res 1988; 12 (5) 419-422
    CrossrefPubMedGoogle Scholar
  • 56 Menell JS, Cesarman GM, Jacovina AT, McLaughlin MA, Lev EA, Hajjar KA. Annexin II and bleeding in acute promyelocytic leukemia. N Engl J Med 1999; 340 (13) 994-1004
    CrossrefPubMedGoogle Scholar
  • 57 O'Connell PA, Madureira PA, Berman JN, Liwski RS, Waisman DM. Regulation of S100A10 by the PML-RAR-α oncoprotein. Blood 2011; 117 (15) 4095-4105
    CrossrefPubMedGoogle Scholar
  • 58 Meijers JC, Oudijk EJ, Mosnier LO , et al. Reduced activity of TAFI (thrombin-activatable fibrinolysis inhibitor) in acute promyelocytic leukaemia. Br J Haematol 2000; 108 (3) 518-523
    CrossrefPubMedGoogle Scholar
  • 59 Kwaan HC, Rego EM. Role of microparticles in the hemostatic dysfunction in acute promyelocytic leukemia. Semin Thromb Hemost 2010; 36 (8) 917-924
    Article in Thieme ConnectPubMedGoogle Scholar
  • 60 Kwaan HC, Rego EM, McMahon B, Weiss I, Marvin J. Microparticles in acute promyelocytic leukemia. Blood 2011; 118: 3346 (Abstract)
    PubMedGoogle Scholar
  • 61 Judicone C, Frankel D, Lacroix R , et al. Microparticles from Acute Promyelocytic Leukemia Generate Plasmin in Urokinase-Dependant Manner. ISTH 2016 SSC. 62, 2016/05/25–28, Montpellier, France; 2016
    PubMedGoogle Scholar