Cell-derived microparticles in haemostasis and vascular medicine

Summary

Considerable interest for cell-derived microparticles has emerged, pointing out their essential role in haemostatic response and their potential as disease markers, but also their implication in a wide range of physiological and pathological processes. They derive from different cell types including platelets – the main source of microparticles – but also from red blood cells, leukocytes and endothelial cells, and they circulate in blood. Despite difficulties encountered in analyzing them and disparities of results obtained with a wide range of methods, microparticle generation processes are now better understood. However, a generally admitted definition of microparticles is currently lacking. For all these reasons we decided to review the literature regarding microparticles in their widest definition, including ectosomes and exosomes, and to focus mainly on their role in haemostasis and vascular medicine.

Keywords

Microparticle - ectosome - haemostasis - vascular pathologies

• References

• 1 Chargaff E, West R. The biological significance of the thromboplastic protein of blood. J Biol Chem 1946; 166: 189-197.
• 2 Wolf P. The nature and significance of platelet products in human plasma. Br J Haematol 1967; 13: 269-288.
• 3 Flaumenhaft R, Dilks JR, Richardson J. et al. Megakaryocyte-derived microparticles: Direct visualization and distinction from platelet-derived microparticles. Blood. 2008 prebub online.
• 4 Cramer EM, Norol F, Guichard J. et al. Ultrastructure of platelet formation by human megakaryocytes cultured with the Mpl ligand. Blood 1997; 89: 2336-2346.
• 5 Rozmyslowicz T, Majka M, Kijowski J. et al. Platelet- and megakaryocyte-derived microparticles transfer CXCR4 receptor to CXCR4-null cells and make them susceptible to infection by X4-HIV. AIDS 2003; 17: 33-42.
• 6 Flaumenhaft R. Formation and fate of platelet microparticles. Blood Cells Mol Dis 2006; 36: 182-187.
• 7 Freyssinet JM. Cellular microparticles: what are they bad or good for?. J Thromb Haemost 2003; 1: 1655-1662.
• 8 VanWijk MJ, VanBavel E, Sturk A. et al. Microparticles in cardiovascular diseases. Cardiovasc Res 2003; 59: 277-287.
• 9 Owens MR. The role of platelet microparticles in hemostasis. Transfusion Med Rev 1994; 8: 37-44.
• 10 Jy W, Horstman LL, Jimenez JJ. et al. Measuring circulating cell-derived microparticles. J Thromb Haemost 2004; 2: 1842-1851.
• 11 Morel O, Morel N, Hugel B. et al. The significance of circulating microparticles in physiology, inflammatory and thrombotic diseases. Rev Med Interne 2005; 26: 791-801.
• 12 Zwaal RFA, Comfurius P, Bevers EM. Platelet procoagulant activity and microvesicle formation. Its putative role in hemostasis and thrombosis. Biochim Biophys Acta – Mol Basis Dis 1992; 1180: 1-8.
• 13 Furie B, Furie BC. Cancer-associated thrombosis. Blood Cells Mol Dis 2006; 36: 177-181.
• 14 Perez-Pujol S, Marker PH, Key NS. Platelet microparticles are heterogeneous and highly dependent on the activation mechanism: studies using a new digital flow cytometer. Cytometry A 2007; 71: 38-45.
• 15 Pilzer D, Gasser O, Moskovich O. et al. Emission of membrane vesicles: roles in complement resistance, immunity and cancer. Springer Semin Immunopathol 2005; 27: 375-387.
• 16 Raposo G, Nijman HW, Stoorvogel W. et al. B lymphocytes secrete antigen-presenting vesicles. J Exp Med 1996; 183: 1161-1172.
• 17 Johnstone RM. Exosomes biological significance: A concise review. Blood Cells Mol Dis 2006; 36: 315-321.
• 18 Scientific Subcommittee Minute.. 51th Annual Scientific and Standardization Committee Meeting. 2005 6–7 August; Sydney, Australia; 2005.
• 19 Scientific Subcommittee Minute.. 54th Annual Scientific and Standardization Committee Meeting. 2008 2–5 July; Vienna, Austria; 2008.
• 20 Fox JEB, Austin CD, Boyles JK. et al. Role of the membrane skeleton in preventing the shedding of procoagulant-rich microvesicles from the platelet plasma membrane. J Cell Biol 1990; 111: 483-493.
• 21 Fox JE, Austin CD, Reynolds CC. et al. Evidence that agonist-induced activation of calpain causes the shedding of procoagulant-containing microvesicles from the membrane of aggregating platelets. J Biol Chem 1991; 266: 13289-13295.
• 22 McLaughlin PJ, Gooch JT, Mannherz HG. et al. Structure of gelsolin segment 1-actin complex and the mechanism of filament severing. Nature 1993; 364: 685-692.
• 23 Basse F, Gaffet P, Bienvenue A. Correlation between inhibition of cytoskeleton proteolysis and anti-vesiculation effect of calpeptin during A23187-induced activation of human platelets: are vesicles shed by filopod fragmentation?. Biochim Biophys Acta 1994; 1190: 217-224.
• 24 Wiedmer T, Shattil SJ, Cunningham M. et al. Role of calcium and calpain in complement-induced vesiculation of the platelet plasma membrane and in the exposure of the platelet factor Va receptor. Biochemistry 1990; 29: 623-632.
• 25 Weerheim AM, Kolb AM, Sturk A. et al. Phospholipid composition of cell-derived microparticles determined by one-dimensional high-performance thin-layer chromatography. Anal Biochem 2002; 302: 191-198.
• 26 Jimenez JJ, Jy W, Mauro LM. et al. Endothelial cells release phenotypically and quantitatively distinct microparticles in activation and apoptosis. Thromb Res 2003; 109: 175-180.
• 27 Miguet L, Pacaud K, Felden C. et al. Proteomic analysis of malignant lymphocyte membrane microparticles using double ionization coverage optimization. Proteomics 2006; 6: 153-171.
• 28 Smalley DM, Root KE, Cho H. et al. Proteomic discovery of 21 proteins expressed in human plasma-derived but not platelet-derived microparticles. Thromb Haemost 2007; 97: 67-80.
• 29 Blanchard N, Lankar D, Faure F. et al. TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/zeta complex. J Immunol 2002; 168: 3235-3241.
• 30 Sims PJ, Wiedmer T, Esmon CT. et al. Assembly of the platelet prothrombinase complex is linked to vesiculation of the platelet plasma membrane. Studies in Scott syndrome: an isolated defect in platelet procoagulant activity. J Biol Chem 1989; 264: 17049-17057.
• 31 Fritzsching B, Schwer B, Kartenbeck J. et al. Release and intercellular transfer of cell surface CD81 via microparticles. J Immunol 2002; 169: 5531-5537.
• 32 Baj-Krzyworzeka M, Szatanek R, Weglarczyk K. et al. Tumour-derived microvesicles carry several surface determinants and mRNA of tumour cells and transfer some of these determinants to monocytes. Cancer Immunol Immunother 2006; 55: 808-818.
• 33 Perini F, Vidal R, Ghetti B. et al. PrP27–30 is a normal soluble prion protein fragment released by human platelets. Biochem Biophys Res Commun 1996; 223: 572-577.
• 34 Robertson C, Booth SA, Beniac DR. et al. Cellular prion protein is released on exosomes from activated platelets. Blood 2006; 107: 3907-3911.
• 35 Crawford N. The presence of contractile proteins in platelet microparticles isolated from human and animal platelet-free plasma. Br J Haematol 1971; 21: 53-69.
• 36 Becker CL, Parker JW, Hechinger MK. Is forward scatter monotonic on commercial flow cytometers?. ISAC XXI Congress; 2002 San Diego, CA, USA: 2002.
• 37 Hugel B, Zobairi F, Freyssinet JM. Measuring circulating cell-derived microparticles. J Thromb Haemost 2004; 2: 1846-1847.
• 38 Shet AS, Aras O, Gupta K. et al. Sickle blood contains tissue factor-positive microparticles derived from endothelial cells and monocytes. Blood 2003; 102: 2678-2683.
• 39 Horstman LL, Jy W, Jimenez JJ. et al. New horizons in the analysis of circulating cell-derived microparticles. Keio J Med 2004; 53: 210-230.
• 40 Aupeix K, Hugel B, Martin T. et al. The significance of shed membrane particles during programmed cell death in vitro, and in vivo, in HIV-1 infection. J Clin Invest 1997; 99: 1546-1554.
• 41 Combes V, Simon AC, Grau GE. et al. In vitro generation of endothelial microparticles and possible prothrombotic activity in patients with lupus anticoagulant. J Clin Invest 1999; 104: 93-102.
• 42 Sims PJ, Faioni EM, Wiedmer T. et al. Complement proteins C5b-9 cause release of membrane vesicles from the platelet surface that are enriched in the membrane receptor for coagulation factor Va and express prothrombinase activity. J Biol Chem 1988; 263: 18205-18212.
• 43 Matzdorff AC, Kuhnel G, Kemkes-Matthes B. et al. Effect of glycoprotein IIb/IIIa inhibitors on CD62p expression, platelet aggregates, and microparticles in vitro. J Lab Clin Med 2000; 135: 247-255.
• 44 Michelson AD, Furman MI. Laboratory markers of platelet activation and their clinical significance. Curr Opin Hematol 1999; 6: 342-348.
• 45 Vidal C, Spaulding C, Picard F. et al. Flow cytometry detection of platelet procoagulation activity and microparticles in patients with unstable angina treated by percutaneous coronary angioplasty and stent implantation. Thromb Haemost 2001; 86: 784-790.
• 46 Xiao H, Jepkorir CJ, Harvey K. et al. Thrombin-induced platelet microparticles improved the aggregability of cryopreserved platelets. Cryobiology 2002; 44: 179-188.
• 47 Toth B, Nikolajek K, Rank A. et al. Gender-specific and menstrual cycle dependent differences in circulating microparticles. Platelets 2007; 18: 515-521.
• 48 Madden LA, Vince RV, Sandstrom ME. et al. Microparticle-associated vascular adhesion molecule-1 and tissue factor follow a circadian rhythm in healthy human subjects. Thromb Haemost 2008; 99: 909-915.
• 49 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: 1585-1598.
• 50 Gross PL, Furie BC, Merrill-Skoloff G. et al. Leukocyte-versus microparticle-mediated tissue factor transfer during arteriolar thrombus development. J Leukoc Biol 2005; 78: 1318-1326.
• 51 Hrachovinová I, Cambien B, Hafezi-Moghadam A. et al. Interaction of P-selectin and PSGL-1 generates microparticles that correct hemostasis in a mouse model of hemophilia A. Nature Med 2003; 9: 1020-1025.
• 52 George JN, Thoi LL, McManus LM. et al. Isolation of human platelet membrane microparticles from plasma and serum. Blood 1982; 60: 834-840.
• 53 Warren BA, Vales O. The adhesive dendritic pseudopodium of the platelet and the release reaction. Microvasc Res 1972; 4: 159-178.
• 54 Horstman LL, Valle-Riestra BJ, Jy W. et al. Desmopressin (DDAVP) acts on platelets to generate platelet microparticles and enhanced procoagulant activity. Thrombosis Res 1995; 79: 163-174.
• 55 Sims PJ, Wiedmer T. Repolarization of the membrane potential of blood platelets after complement damage: Evidence for a Ca++-dependent exocytotic elimination of C5b-9 pores. Blood 1986; 68: 557-561.
• 56 Wiedmer T, Sims PJ. Effect of complement proteins C5b-9 on blood platelets. Evidence for reversible depolarization of membrane potential. J Biol Chem 1985; 260: 8014-8019.
• 57 Hamilton KK, Hattori R, Esmon CT. et al. Complement proteins C5b-9 induce vesiculation of the endothelial plasma membrane and expose catalytic surface for assembly of the prothrombinase enzyme complex. J Biol Chem 1990; 265: 3809-3814.
• 58 Nomura S, Yanabu M, Kido H. et al. Significance of cytokines and CD68-positive microparticles in Immune thrombocytopenic purpura. Eur J Haematol 1995; 55: 49-56.
• 59 Nomura S, Nakamura T, Cone J. et al. Cytometric analysis of high shear-induced platelet microparticles and effect of cytokines on microparticle generation. Cytometry 2000; 40: 173-181.
• 60 Martinez-Lorenzo MJ, Anel A, Gamen S. et al. Activated human T cells release bioactive Fas ligand and APO2 ligand in microvesicles. J Immunol 1999; 163: 1274-1281.
• 61 Horstman LL, Ahn YS. Platelet microparticles: a wide-angle perspective. Crit Rev Oncol Hematol 1999; 30: 111-142.
• 62 Heijnen HF, Schiel AE, Fijnheer R. et al. Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha-granules. Blood 1999; 94: 3791-3799.
• 63 Warren BA, Vales O. The release of vesicles from platelets following adhesion to vessel walls in vitro. Br J Exp Pathol 1972; 53: 206-215.
• 64 Miyazaki Y, Nomura S, Miyake T. et al. High shear stress can initiate both platelet aggregation and shedding of procoagulant containing microparticles. Blood 1996; 88: 3456-3464.
• 65 Holme PA, Solum NO, Brosstad FR. et al. Shear-induced platelet activation and platelet microparticle formation at blood flow conditions as in arteries with a severe stenosis. Arteriosclerosis Thromb Vasc Biol 1997; 17: 646-653.
• 66 Ikeda M, Iwamoto S, Imamura H. et al. Increased platelet aggregation and production of platelet-derived microparticles after surgery for upper gastrointestinal malignancy. J Surg Res 2003; 115: 174-183.
• 67 Reininger AJ, Heijnen HF, Schumann H. et al. Mechanism of platelet adhesion to von Willebrand factor and microparticle formation under high shear stress. Blood 2006; 107: 3537-3545.
• 68 Fox JEB. The platelet cytoskeleton. Thromb Haemost 1993; 70: 884-893.
• 69 Rand ML, Wang H, Bang KW. et al. Rapid clearance of procoagulant platelet-derived microparticles from the circulation of rabbits. J Thromb Haemost 2006; 4: 1621-1623.
• 70 Fourcade O, Simon MF, Viode C. et al. Secretory phospholipase A2 generates the novel lipid mediator lysophosphatidic acid in membrane microvesicles shed from activated cells. Cell 1995; 80: 919-927.
• 71 Wu Y, Tibrewal N, Birge RB. Phosphatidylserine recognition by phagocytes: a view to a kill. Trends Cell Biol 2006; 16: 189-197.
• 72 Willekens FL, Werre JM, Kruijt JK. et al. Liver Kupffer cells rapidly remove red blood cell-derived vesicles from the circulation by scavenger receptors. Blood 2005; 105: 2141-2145.
• 73 Sinauridze EI, Kireev DA, Popenko NY. et al. Platelet microparticle membranes have 50– to 100-fold higher specific procoagulant activity than activated platelets. Thromb Haemost 2007; 97: 425-434.
• 74 Tans G, Rosing J, Thomassen MCLGD. et al. Comparison of anticoagulant and procoagulant activities of stimulated platelets and platelet-derived microparticles. Blood 1991; 77: 2641-2648.
• 75 Bach R, Rifkin DB. Expression of tissue factor procoagulant activity: regulation by cytosolic calcium. Proc Natl Acad Sci USA 1990; 87: 6995-6999.
• 76 Maynard JR, Heckman CA, Pitlick FA. et al. Association of tissue factor activity with the surface of cultured cells. J Clin Invest 1975; 55: 814-824.
• 77 Stone MD, Harvey SB, Martinez MB. et al. Large enhancement of functional activity of active site-inhibited factor VIIa due to protein dimerization: insights into mechanism of assembly/disassembly from tissue factor. Biochemistry 2005; 44: 6321-6330.
• 78 Dietzen DJ, Page KL, Tetzloff TA. Lipid rafts are necessary for tonic inhibition of cellular tissue factor procoagulant activity. Blood 2004; 103: 3038-3044.
• 79 Osterud B. The role of platelets in decrypting monocyte tissue factor. Semin Hematol 2001; 38 (04) (Suppl. 12) 2-5.
• 80 Chen VM, Ahamed J, Versteeg HH. et al. Evidence for activation of tissue factor by an allosteric disulfide bond. Biochemistry 2006; 45: 12020-1208.
• 81 Reinhardt C, von Bruhl ML, Manukyan D. et al. Protein disulfide isomerase acts as an injury response signal that enhances fibrin generation via tissue factor activation. J Clin Invest 2008; 118: 1110-1122.
• 82 Cho J, Furie BC, Coughlin SR. et al. A critical role for extracellular protein disulfide isomerase during thrombus formation in mice. J Clin Invest 2008; 118: 1123-1131.
• 83 Giesen PL, Rauch U, Bohrmann B. et al. Blood-borne tissue factor: another view of thrombosis. Proc Natl Acad Sci USA 1999; 96: 2311-2315.
• 84 Rauch U, Bonderman D, Bohrmann B. et al. Transfer of tissue factor from leukocytes to platelets is mediated by CD15 and tissue factor. Blood 2000; 96: 170-175.
• 85 Holme PA, Solum NO, Brosstad F. et al. Microvesicles bind soluble fibrinogen, adhere to immobilized fibrinogen and coaggregate with platelets. Thromb Haemost 1998; 79: 389-394.
• 86 Nomura S, Xie GL, Katsura K. et al. Participation of ?IIb?3 in platelet microparticle generation by collagen plus thrombin. Haemostasis 1996; 26: 31-37.
• 87 Nomura S, Yanabu M, Miyake T. et al. Relationship of microparticles with ?2-glycoprotein I and P-selectin positivity to anticardiolipin antibodies in immune thrombocytopenic purpura. Ann Hematol 1995; 70: 25-30.
• 88 Nomura S, Tandon NN, Nakamura T. et al. High-shear-stress-induced activation of platelets and microparticles enhances expression of cell adhesion molecules in THP-1 and endothelial cells. Atherosclerosis 2001; 158: 277-287.
• 89 Mause SF, von Hundelshausen P, Zernecke A. et al. Platelet microparticles: a transcellular delivery system for RANTES promoting monocyte recruitment on endothelium. Arterioscler Thromb Vasc Biol 2005; 25: 1512-1518.
• 90 Barry OP, Pratico D, Lawson JA. et al. Transcellular activation of platelets and endothelial cells by bioactive lipids in platelet microparticles. J Clin Invest 1997; 99: 2118-2127.
• 91 Pfister SL. Role of platelet microparticles in the production of thromboxane by rabbit pulmonary artery. Hypertension 2004; 43: 428-433.
• 92 Amabile N, Guerin AP, Leroyer A. et al. Circulating endothelial microparticles are associated with vascular dysfunction in patients with end-stage renal failure. J Am Soc Nephrol 2005; 16: 3381-3388.
• 93 Boulanger CM, Scoazec A, Ebrahimian T. et al. Circulating microparticles from patients with myocardial infarction cause endothelial dysfunction. Circulation 2001; 104: 2649-2652.
• 94 Castaman G, Yu-Feng L, Battistin E. et al. Characterization of a novel bleeding disorder with isolated prolonged bleeding time and deficiency of platelet microvesicle generation. Br J Haematol 1997; 96: 458-463.
• 95 Castaman G, Yu-Feng L, Rodeghiero F. A bleeding disorder characterised by isolated deficiency of platelet microvesicle generation. Lancet 1996; 347: 700-701.
• 96 Martinez MC, Martin S, Toti F. et al. Significance of capacitative Ca2+ entry in the regulation of phosphatidylserine expression at the surface of stimulated cells. Biochemistry 1999; 38: 10092-10098.
• 97 Venkatachalam K, van Rossum DB, Patterson RL. et al. The cellular and molecular basis of store-operated calcium entry. Nat Cell Biol 2002; 4: E263-272.
• 98 Bevers EM, Wiedmer T, Comfurius P. et al. The complex of phosphatidylinositol 4,5-bisphosphate and calcium ions is not responsible for Ca2+-induced loss of phospholipid asymmetry in the human erythrocyte: a study in Scott syndrome, a disorder of calcium-induced phospholipid scrambling. Blood 1995; 86: 1983-1991.
• 99 Zwaal RF, Comfurius P, Bevers EM. Scott syndrome, a bleeding disorder caused by defective scrambling of membrane phospholipids. Biochim Biophys Acta 2004; 1636: 119-128.
• 100 Albrecht C, McVey JH, Elliott JI. et al. A novel missense mutation in ABCA1 results in altered protein trafficking and reduced phosphatidylserine trans-location in a patient with Scott syndrome. Blood 2005; 106: 542-549.
• 101 Stormorken H, Holmsen H, Sund R. et al. Studies on the haemostatic defect in a complicated syndrome. An inverse Scott syndrome platelet membrane abnormality? Thromb Haemost 1995; 74: 1244-1251.
• 102 Chirinos JA, Heresi GA, Velasquez H. et al. Elevation of endothelial microparticles, platelets, and leukocyte activation in patients with venous thromboembolism. J Am Coll Cardiol 2005; 45: 1467-1471.
• 103 Steppich B, Mattisek C, Sobczyk D. et al. Tissue factor pathway inhibitor on circulating microparticles in acute myocardial infarction. Thromb Haemost 2005; 93: 35-39.
• 104 Wakefield TW, Henke PK. The role of inflammation in early and late venous thrombosis: Are there clinical implications?. Semin Vasc Surg 2005; 18: 118-129.
• 105 Amiral J, Bridey F, Dreyfus M. et al. Platelet factor 4 complexed to heparin is the target for antibodies generated in heparin-induced thrombocytopenia. Thromb Haemost 1992; 68: 95-96.
• 106 Kelton JG, Sheridan D, Santos A. et al. Heparin-induced thrombocytopenia: laboratory studies. Blood 1988; 72: 925-930.
• 107 Warkentin TE, Hayward CPM, Boshkov LK. et al. Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: An explanation for the thrombotic complications of heparin-induced thrombocytopenia. Blood 1994; 84: 3691-3699.
• 108 Hughes M, Hayward CP, Warkentin TE. et al. Morphological analysis of microparticle generation in heparin-induced thrombocytopenia. Blood 2000; 96: 188-194.
• 109 Dignat-George F, Camoin-Jau L, Sabatier F. et al. Endothelial microparticles: a potential contribution to the thrombotic complications of the antiphospholipid syndrome. Thromb Haemost 2004; 91: 667-673.
• 110 Morel O, Jesel L, Freyssinet JM. et al. Elevated levels of procoagulant microparticles in a patient with myocardial infarction, antiphospholipid antibodies and multifocal cardiac thrombosis. Thromb J 2005; 3: 15.
• 111 Jy W, Tiede M, Bidot CJ. et al. Platelet activation rather than endothelial injury identifies risk of thrombosis in subjects positive for antiphospholipid antibodies. Thromb Res 2007; 121: 319-325.
• 112 Ambrozic A, Bozic B, Kveder T. et al. Budding, vesiculation and permeabilization of phospholipid membranes-evidence for a feasible physiologic role of beta2-glycoprotein I and pathogenic actions of anti-beta2-glycoprotein I antibodies. Biochim Biophys Acta 2005; 1740: 38-44.
• 113 Kelton JG, Warkentin TE, Hayward CP. et al. Calpain activity in patients with thrombotic thrombocytopenic purpura is associated with platelet microparticles. Blood 1992; 80: 2246-2251.
• 114 Jimenez JJ, Jy W, Mauro LM. et al. Elevated endothelial microparticles in thrombotic thrombocytopenic purpura: findings from brain and renal microvascular cell culture and patients with active disease. Br J Haematol 2001; 112: 81-90.
• 115 Hugel B, Socie G, Vu T. et al. Elevated levels of circulating procoagulant microparticles in patients with paroxysmal nocturnal hemoglobinuria and aplastic anemia. Blood 1999; 93: 3451-3456.
• 116 Butikofer P, Kuypers FA, Xu CM. et al. Enrichment of two glycosyl-phosphatidylinositol-anchored proteins, acetylcholinesterase and decay accelerating factor, in vesicles released from human red blood cells. Blood 1989; 74: 1481-1485.
• 117 Wiedmer T, Hall SE, Ortel TL. et al. Complement-induced vesiculation and exposure of membrane prothrombinase sites in platelets of paroxysmal nocturnal hemoglobinuria. Blood 1993; 82: 1192-1196.
• 118 Sims PJ, Wiedmer T. The response of human platelets to activated components of the complement system. Immunol Today 1991; 12: 338-342.
• 119 Adams GT, Snieder H, McKie VC. et al. Genetic risk factors for cerebrovascular disease in children with sickle cell disease: design of a case-control association study and genomewide screen. BMC Med Genet 2003; 4: 6.
• 120 Bunn HF. Pathogenesis and treatment of sickle cell disease. N Engl J Med 1997; 337: 762-769.
• 121 Wun T, Paglieroni T, Rangaswami A. et al. Platelet activation in patients with sickle cell disease. Br J Haematol 1998; 100: 741-749.
• 122 Wun T, Paglieroni T, Tablin F. et al. Platelet activation and platelet-erythrocyte aggregates in patients with sickle cell anemia. J Lab Clin Med 1997; 129: 507-516.
• 123 Allan D, Limbrick AR, Thomas P. et al. Release of spectrin-free spicules on reoxygenation of sickled erythrocytes. Nature 1982; 295: 612-613.
• 124 Brill A, Elinav H, Varon D. Differential role of platelet granular mediators in angiogenesis. Cardiovasc Res 2004; 63: 226-235.
• 125 Kim HK, Song KS, Chung JH. et al. Platelet microparticles induce angiogenesis in vitro. Br J Haematol 2004; 124: 376-384.
• 126 Brill A, Dashevsky O, Rivo J. et al. Platelet-derived microparticles induce angiogenesis and stimulate post-ischemic revascularization. Cardiovasc Res 2005; 67: 30-38.
• 127 Nguyen M, Arkell J, Jackson CJ. Active and tissue inhibitor of matrix metalloproteinase-free gelatinase B accumulates within human microvascular endothelial vesicles. J Biol Chem 1998; 273: 5400-5404.
• 128 Taraboletti G, D’Ascenzo S, Borsotti P. et al. Shedding of the matrix metalloproteinases MMP-2, MMP-9, and MT1-MMP as membrane vesicle-associated components by endothelial cells. Am J Pathol 2002; 160: 673-680.
• 129 Mezentsev A, Merks RM, O’Riordan E. et al. Endothelial microparticles affect angiogenesis in vitro: role of oxidative stress. Am J Physiol Heart Circ Physiol 2005; 289: H1106-1114.
• 130 Agouni A, Mostefai HA, Porro C. et al. Sonic hedgehog carried by microparticles corrects endothelial injury through nitric oxide release. FASEB J 2007; 21: 2735-2741.
• 131 Mostefai HA, Agouni A, Carusio N. et al. Phosphatidylinositol 3-kinase and xanthine oxidase regulate nitric oxide and reactive oxygen species productions by apoptotic lymphocyte microparticles in endothelial cells. J Immunol 2008; 180: 5028-5035.
• 132 Yang C, Mwaikambo BR, Zhu T. et al. Lymphocytic microparticles inhibit angiogenesis by stimulating oxidative stress and negatively regulating VEGF-induced pathways. Am J Physiol Regul Integr Comp Physiol 2008; 294: R467-476.
• 133 Preston RA, Jy W, Jimenez JJ. et al. Effects of severe hypertension on endothelial and platelet microparticles. Hypertension 2003; 41: 211-217.
• 134 Amabile N, Heiss C, Real WM. et al. Circulating endothelial microparticle levels predict hemodynamic severity of pulmonary hypertension. Am J Respir Crit Care Med 2008; 177: 1268-1275.
• 135 Bakouboula B, Morel O, Faure A. et al. Procoagulant membrane microparticles correlate with the severity of pulmonary arterial hypertension. Am J Respir Crit Care Med 2008; 177: 536-543.
• 136 Bonderman D, Teml A, Jakowitsch J. et al. Coronary no-reflow is caused by shedding of active tissue factor from dissected atherosclerotic plaque. Blood 2002; 99: 2794-2800.
• 137 Barry OP, Pratico D, Savani RC. et al. Modulation of monocyte-endothelial cell interactions by platelet microparticles. J Clin Invest 1998; 102: 136-144.
• 138 Mantovani A, Dejana E. Cytokines as communication signals between leukocytes and endothelial cells. Immunol Today 1989; 10: 370-375.
• 139 Issekutz TB, Issekutz AC, Movat HZ. The in vivo quantitation and kinetics of monocyte migration into acute inflammatory tissue. Am J Pathol 1981; 103: 47-55.
• 140 Kockx MM. Apoptosis in the atherosclerotic plaque: quantitative and qualitative aspects. Arterioscler Thromb Vasc Biol 1998; 18: 1519-1522.
• 141 Leroyer AS, Isobe H, Leseche G. et al. Cellular origins and thrombogenic activity of microparticles isolated from human atherosclerotic plaques. J Am Coll Cardiol 2007; 49: 772-777.
• 142 Kolodgie FD, Narula J, Burke AP. et al. Localization of apoptotic macrophages at the site of plaque rupture in sudden coronary death. Am J Pathol 2000; 157: 1259-1268.
• 143 Mallat Z, Hugel B, Ohan J. et al. Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques: a role for apoptosis in plaque thrombogenicity. Circulation 1999; 99: 348-353.
• 144 Nomura S, Imamura A, Okuno M. et al. Platelet-derived microparticles in patients with arteriosclerosis obliterans: enhancement of high shear-induced micro-particle generation by cytokines. Thromb Res 2000; 98: 257-268.
• 145 Boulanger CM, Amabile N, Tedgui A. Circulating microparticles: a potential prognostic marker for atherosclerotic vascular disease. Hypertension 2006; 48: 180-186.
• 146 Mallat Z, Benamer H, Hugel B. et al. Elevated levels of shed membrane microparticles with procoagulant potential in the peripheral circulating blood of patients with acute coronary syndromes. Circulation 2000; 101: 841-843.
• 147 Werner N, Wassmann S, Ahlers P. et al. Circulating CD31+/annexin V+ apoptotic microparticles correlate with coronary endothelial function in patients with coronary artery disease. Arterioscler Thromb Vasc Biol 2006; 26: 112-116.
• 148 Heloire F, Weill B, Weber S. et al. Aggregates of endothelial microparticles and platelets circulate in peripheral blood. Variations during stable coronary disease and acute myocardial infarction. Thromb Res 2003; 110: 173-180.
• 149 Bernal-Mizrachi L, Jy W, Fierro C. et al. Endothelial microparticles correlate with high-risk angio-graphic lesions in acute coronary syndromes. Int J Cardiol 2004; 97: 439-446.
• 150 Chung J, Suzuki H, Tabuchi N. et al. Identification of tissue factor and platelet-derived particles on leukocytes during cardiopulmonary bypass by flow cytometry and immunoelectron microscopy. Thromb Haemost 2007; 98: 368-374.
• 151 Nieuwland R, Berckmans RJ, Rotteveel-Eijkman RC. et al. Cell-derived microparticles generated in patients during cardiopulmonary bypass are highly procoagulant. Circulation 1997; 96: 3534-3541.
• 152 Johnell M, Elgue G, Thelin S. et al. Cell adhesion and tissue factor upregulation in oxygenators used during coronary artery bypass grafting are modified by the Corline Heparin Surface. Scand Cardiovasc J 2002; 36: 351-357.
• 153 Craft JA, Masci PP, Roberts MS. et al. Increased platelet-derived microparticles in the coronary circulation of percutaneous transluminal coronary angioplasty patients. Blood Coagul Fibrinolysis 2004; 15: 475-482.
• 154 Bernard GR, Vincent JL, Laterre PF. et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001; 344: 699-709.
• 155 Galligan L, Livingstone W, Volkov Y. et al. Characterization of protein C receptor expression in monocytes. Br J Haematol 2001; 115: 408-414.
• 156 Perez-Casal M, Downey C, Fukudome K. et al. Activated protein C induces the release of microparticle-associated endothelial protein C receptor. Blood 2005; 105: 1515-1522.
• 157 Abraham E, Wunderink R, Silverman H. et al. Efficacy and safety of monoclonal antibody to human tumor necrosis factor alpha in patients with sepsis syndrome. A randomized, controlled, double-blind, multi-center clinical trial. TNF-alpha MAb Sepsis Study Group. J Am Med Assoc 1995; 273: 934-941.
• 158 Fisher Jr CJ, Agosti JM, Opal SM. et al. Treatment of septic shock with the tumor necrosis factor receptor:Fc fusion protein. The Soluble TNF Receptor Sepsis Study Group. N Engl J Med 1996; 334: 1697-1702.
• 159 Nieuwland R, Berckmans RJ, McGregor S. et al. Cellular origin and procoagulant properties of microparticles in meningococcal sepsis. Blood 2000; 95: 930-935.
• 160 Callens S, Florence E, Philippe M. et al. Mixed arterial and venous thromboembolism in a person with HIV infection. Scand J Infect Dis 2003; 35: 907-908.
• 161 Jansen JM, Lijfering WM, Sprenger HG. et al. Venous thromboembolism in HIV-positive women during puerperium: a case series. Blood Coagul Fibrinolysis 2008; 19: 95-97.
• 162 Cota-Gomez A, Flores NC, Cruz C. et al. The human immunodeficiency virus-1 Tat protein activates human umbilical vein endothelial cell E-selectin expression via an NF-kappa B-dependent mechanism. J Biol Chem 2002; 277: 14390-14399.
• 163 Martin S, Tesse A, Hugel B. et al. Shed membrane particles from T lymphocytes impair endothelial function and regulate endothelial protein expression. Circulation 2004; 109: 1653-1659.
• 164 Zelivianski S, Liang D, Chen M. et al. Suppressive effect of elongation factor 2 on apoptosis induced by HIV-1 viral protein R. Apoptosis 2006; 11: 377-388.
• 165 Gris JC, Toulon P, Brun S. et al. The relationship between plasma microparticles, protein S and anticardiolipin antibodies in patients with human immunodeficiency virus infection. Thromb Haemost 1996; 76: 38-45.
• 166 Mack M, Kleinschmidt A, Bruhl H. et al. Transfer of the chemokine receptor CCR5 between cells by membrane-derived microparticles: a mechanism for cellular human immunodeficiency virus 1 infection. Nat Med 2000; 6: 769-775.
• 167 Janowska-Wieczorek A, Majka M, Kijowski J. et al. Platelet-derived microparticles bind to hematopoietic stem/progenitor cells and enhance their engraftment. Blood 2001; 98: 3143-3149.
• 168 Fevrier B, Vilette D, Archer F. et al. Cells release prions in association with exosomes. Proc Natl Acad Sci USA 2004; 101: 9683-9688.
• 169 Cervenakova L, Yakovleva O, McKenzie C. et al. Similar levels of infectivity in the blood of mice infected with human-derived vCJD and GSS strains of transmissible spongiform encephalopathy. Transfusion 2003; 43: 1687-1694.
• 170 Ratajczak J, Miekus K, Kucia M. et al. Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia 2006; 20: 847-856.
• 171 Aliotta JM, Sanchez-Guijo FM, Dooner GJ. et al. Alteration of marrow cell gene expression, protein production, and engraftment into lung by lung-derived microvesicles: a novel mechanism for phenotype modulation. Stem Cells 2007; 25: 2245-2256.
• 172 Deregibus MC, Cantaluppi V, Calogero R. et al. Endothelial progenitor cell derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA. Blood 2007; 110: 2440-2448.
• 173 Valadi H, Ekstrom K, Bossios A. et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007; 9: 654-659.
• 174 Gelderman MP, Simak J. Flow cytometric analysis of cell membrane microparticles. Methods Mol Biol 2008; 484: 79-93.
• 175 Abid Hussein MN, Meesters EW, Osmanovic N. et al. Antigenic characterization of endothelial cell-derived microparticles and their detection ex vivo. J Thromb Haemost 2003; 1: 2434-2443.
• 176 Berckmans RJ, Neiuwland R, Boing AN. et al. Cell-derived microparticles circulate in healthy humans and support low grade thrombin generation. Thromb Haemost 2001; 85: 639-646.
• 177 Sims PJ, Wiedmer T. The response of human platelets to activated components of the complement system. Immunol Today 1991; 12: 338-342.