Semin Thromb Hemost 2008; 34(7): 683-691
DOI: 10.1055/s-0028-1104547
© Thieme Medical Publishers

Microparticles in Health and Disease

Anoop K. Enjeti1 , Lisa F. Lincz1 , Michael Seldon1
  • 1Department of Haematology level 4, Hunter Haematology Research Group, New Medical Building, Calvary Mater Hospital, Waratah Newcastle, Australia
Further Information

Publication History

Publication Date:
15 December 2008 (online)

ABSTRACT

Microparticles (MPs) are small fragments of membrane-bound cytoplasm that are shed from the surface of an activated or apoptotic cell. Recently, their function as vectors of transcellular exchange of biologic information, in addition to better described forms of intercellular communication such as growth factors, cytokines, and chemokines, has become well recognized. Circulating levels of MPs are thought to reflect a balance between cell stimulation, proliferation, and death. The production of MPs is thought to predominately occur by vesiculation or blebbing of the cell membrane. The mechanisms governing the remodeling of the plasma membrane are complex, involving cytoskeletal changes and a shift from normal phospholipid asymmetry. Increased intracellular calcium subsequent to cell activation leads to intracellular increases in several proteins including gelsolin and calpain, as well as the activity of enzymes such as translocase, floppase, and scramblase, which play important roles in the homeostasis of the cell membrane. The membrane vesiculation and phospholipids asymmetry leading to the production of MPs occurs by the complex interplay of the proteins involved. There are several clinical conditions associated with elevated MPs, and most are also associated with an increased risk of thrombosis. Apart from cardiovascular disease and venous thromboembolism, MPs are also elevated in solid tumors with metastatic disease. The measurement of MPs is being regarded as a potential biomarker, given the range of conditions in which they are elevated and the association with prothrombotic states. The utility of measuring MPs as a diagnostic and prognostic marker is currently a subject of intense investigation. The further development of the various methods for the detection and measurement of MPs and prospective clinical trials establishing the utility of such tests will be critical prior to the routine measurement of MPs in the diagnostic laboratory.

REFERENCES

  • 1 Papadimitriou J C, Drachenberg C B, Brenner D S, Newkirk C, Trump B F, Silverberg S G. “Thanatosomes”: a unifying morphogenetic concept for tumor hyaline globules related to apoptosis.  Hum Pathol. 2000;  31 1455-1465
  • 2 Dikov D I, Auriault M L, Boivin J F, Sarafian V S, Papadimitriou J C. Hyaline globules (thanatosomes) in gastrointestinal epithelium: pathophysiologic correlations.  Am J Clin Pathol. 2007;  127 792-799
  • 3 Dikov D, Roland J, Chatelet F P, Cywiner-Golenzer C, Dimitrakov J. Hyaline globules (thanatosomes) in prostate disease.  Am J Surg Pathol. 2003;  27 700-702
  • 4 Beranek J T. Thanatosomes and cardiomyocyte apoptotic bodies.  Hum Pathol. 2001;  32 894-895
  • 5 Ahn Y S. Cell-derived microparticles: 'miniature envoys with many faces'.  J Thromb Haemost. 2005;  3 884-887
  • 6 Greenwalt T J. The how and why of exocytic vesicles.  Transfusion. 2006;  46 143-152
  • 7 Freyssinet J M. Cellular microparticles: what are they bad or good for?.  J Thromb Haemost. 2003;  1 1655-1662
  • 8 Diaz C, Schroit A J. Role of translocases in the generation of phosphatidylserine asymmetry.  J Membr Biol. 1996;  151 1-9
  • 9 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
  • 10 Chou J, Mackman N, Merrill-Skoloff G, Pedersen B, Furie B C, Furie B. Hematopoietic cell-derived microparticle tissue factor contributes to fibrin formation during thrombus propagation.  Blood. 2004;  104 3190-3197
  • 11 Horstman L L, Jy W, Jimenez J J, Bidot C, Ahn Y S. New horizons in the analysis of circulating cell-derived microparticles.  Keio J Med. 2004;  53 210-230
  • 12 Jacoby R C, Owings J T, Holmes J, Battistella F D, Gosselin R C, Paglieroni T G. Platelet activation and function after trauma.  J Trauma. 2001;  51 639-647
  • 13 Morel N, Morel O, Delabranche X et al.. Microparticles during sepsis and trauma. A link between inflammation and thrombotic processes.  Ann Fr Anesth Reanim. 2006;  25 955-966
  • 14 Ardoin S P, Shanahan J C, Pisetsky D S. The role of microparticles in inflammation and thrombosis.  Scand J Immunol. 2007;  66 159-165
  • 15 Schouten M, Wiersinga W J, Levi M, van der Poll T. Inflammation, endothelium, and coagulation in sepsis.  J Leukoc Biol. 2008;  83 536-545
  • 16 Chirinos J A, Heresi G A, 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
  • 17 Barry O P, Pratico D, Savani R C, FitzGerald G A. Modulation of monocyte-endothelial cell interactions by platelet microparticles.  J Clin Invest. 1998;  102 136-144
  • 18 Rectenwald J E, Myers Jr D D, Hawley A E et al.. D-dimer, P-selectin, and microparticles: novel markers to predict deep venous thrombosis. A pilot study.  Thromb Haemost. 2005;  94 1312-1317
  • 19 Chirinos J A, Castrellon A, Zambrano J P et al.. Digoxin use is associated with increased platelet and endothelial cell activation in patients with nonvalvular atrial fibrillation.  Heart Rhythm. 2005;  2 525-529
  • 20 Andres E, Goichot B. Metabolic syndrome and venous thrombosis: potential role of microparticles.  Haematologica. 2007;  92 e64 , author reply e65
  • 21 Myers D D, Hawley A E, Farris D M et al.. P-selectin and leukocyte microparticles are associated with venous thrombogenesis.  J Vasc Surg. 2003;  38 1075-1089
  • 22 Pattanapanyasat K, Noulsri E, Fucharoen S et al.. Flow cytometric quantitation of red blood cell vesicles in thalassemia.  Cytometry B Clin Cytom. 2004;  57 23-31
  • 23 Simak J, Holada K, Risitano A M, Zivny J H, Young N S, Vostal J G. Elevated circulating endothelial membrane microparticles in paroxysmal nocturnal haemoglobinuria.  Br J Haematol. 2004;  125 804-813
  • 24 Tomer A, Harker L A, Kasey S, Eckman J R. Thrombogenesis in sickle cell disease.  J Lab Clin Med. 2001;  137 398-407
  • 25 Cihan A Y, Pabinger I. Metabolic syndrome and venous thrombosis: potential role of microparticles.  Haematologica. 2007;  92 e065
  • 26 Preston R A, Jy W, Jimenez J J et al.. Effects of severe hypertension on endothelial and platelet microparticles.  Hypertension. 2003;  41 211-217
  • 27 Meerarani P, Moreno P R, Cimmino G, Badimon J J. Atherothrombosis: role of tissue factor; link between diabetes, obesity and inflammation.  Indian J Exp Biol. 2007;  45 103-110
  • 28 Horstman L L, Jy W, Jimenez J J, Ahn Y S. Endothelial microparticles as markers of endothelial dysfunction.  Front Biosci. 2004;  9 1118-1135
  • 29 Li M, Goto S, Sakai H et al.. Enhanced shear-induced von Willebrand factor binding to platelets in acute myocardial infarction.  Thromb Res. 2000;  100 251-261
  • 30 Miyamoto S, Marcinkiewicz C, Edmunds Jr L H, Niewiarowski S. Measurement of platelet microparticles during cardiopulmonary bypass by means of captured ELISA for GPIIb/IIIa.  Thromb Haemost. 1998;  80 225-230
  • 31 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;  90 511-518
  • 32 Singh N, Gemmell C H, Daly P A, Yeo E L. Elevated platelet-derived microparticle levels during unstable angina.  Can J Cardiol. 1995;  11 1015-1021
  • 33 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
  • 34 Morel O, Jesel L, Freyssinet J M, Toti F. Elevated levels of procoagulant microparticles in a patient with myocardial infarction, antiphospholipid antibodies and multifocal cardiac thrombosis.  Thromb J. 2005;  3 15
  • 35 Morel O, Toti F, Bakouboula B, Grunebaum L, Freyssinet J M. Procoagulant microparticles: ‘criminal partners’ in atherothrombosis and deleterious cellular exchanges.  Pathophysiol Haemost Thromb. 2006;  35 15-22
  • 36 Geiser T, Sturzenegger M, Genewein U, Haeberli A, Beer J H. Mechanisms of cerebrovascular events as assessed by procoagulant activity, cerebral microemboli, and platelet microparticles in patients with prosthetic heart valves.  Stroke. 1998;  29 1770-1777
  • 37 Exner T, Joseph J E, Connor D, Low J, Ma D D. Increased procoagulant phospholipid activity in blood from patients with suspected acute coronary syndromes: a pilot study.  Blood Coagul Fibrinolysis. 2005;  16 375-379
  • 38 Namba M, Tanaka A, Shimada K et al.. Circulating platelet-derived microparticles are associated with atherothrombotic events: a marker for vulnerable blood.  Arterioscler Thromb Vasc Biol. 2007;  27 255-256
  • 39 Tan K T, Tayebjee M H, Lynd C, Blann A D, Lip G Y. Platelet microparticles and soluble P selectin in peripheral artery disease: relationship to extent of disease and platelet activation markers.  Ann Med. 2005;  37 61-66
  • 40 Weber C A, Matzdorff A C, Gerriets T, Villmow T, Stolz E. Circulating microemboli in patients with myeloproliferative disorders.  Eur J Neurol. 2007;  14 199-205
  • 41 Villmow T, Kemkes-Matthes B, Matzdorff A C. Markers of platelet activation and platelet-leukocyte interaction in patients with myeloproliferative syndromes.  Thromb Res. 2002;  108 139-145
  • 42 Kelton J G, Warkentin T E, Hayward C P, Murphy W G, Moore J C. Calpain activity in patients with thrombotic thrombocytopenic purpura is associated with platelet microparticles.  Blood. 1992;  80 2246-2251
  • 43 Nomura S, Ishii K, Kanazawa S et al.. Significance of elevation in cell-derived microparticles after allogeneic stem cell transplantation: transient elevation of platelet-derived microparticles in TMA/TTP.  Bone Marrow Transplant. 2005;  36 921-922
  • 44 Warkentin T E, Hayward C P, Boshkov L K 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
  • 45 Warkentin T E. Heparin-induced thrombocytopenia: a ten-year retrospective.  Annu Rev Med. 1999;  50 129-147
  • 46 Brenner B. Haemostatic changes in pregnancy.  Thromb Res. 2004;  114 409-414
  • 47 Gonzalez-Quintero V H, Jimenez J J, Jy W et al.. Elevated plasma endothelial microparticles in preeclampsia.  Am J Obstet Gynecol. 2003;  189 589-593
  • 48 Laude I, Rongieres-Bertrand C, Boyer-Neumann C et al.. Circulating procoagulant microparticles in women with unexplained pregnancy loss: a new insight.  Thromb Haemost. 2001;  85 18-21
  • 49 Uszynski M. Problems of recurrent loss of pregnancy: are procoagulant microparticles a risk factor for pregnancy outcome?.  Ginekol Pol. 2004;  75 642-648
  • 50 Carp H, Dardik R, Lubetsky A et al.. Prevalence of circulating procoagulant microparticles in women with recurrent miscarriage: a case-controlled study.  Hum Reprod. 2004;  19 191-195
  • 51 Greer I A. Endothelial cell microparticles and antiphospholipid syndrome: pathologic explanations and diagnostic opportunities.  Thromb Haemost. 2004;  91 636-638
  • 52 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
  • 53 Bidot C J, Jy W, Horstman L L et al.. Antiphospholipid antibodies and platelet activation as risk factors for thrombosis in thrombocythaemia.  Hematology.. 2005;  10 451-456
  • 54 Pereira J, Alfaro G, Goycoolea M et al.. Circulating platelet-derived microparticles in systemic lupus erythematosus. Association with increased thrombin generation and procoagulant state.  Thromb Haemost. 2006;  95 94-99
  • 55 Combes V, Simon A C, Grau G E et al.. In vitro generation of endothelial microparticles and possible prothrombotic activity in patients with lupus anticoagulant.  J Clin Invest. 1999;  104 93-102
  • 56 George J N, Pickett E B, Heinz R. Platelet membrane glycoprotein changes during the preparation and storage of platelet concentrates.  Transfusion. 1988;  28 123-126
  • 57 Scharf R E, Hanfland P. Platelet storage lesions: analysis of platelet membrane glycoproteins and platelet-derived microparticles by fluorescence-activated flow cytometry.  Transfus Sci. 1993;  14 189-194
  • 58 Simak J, Gelderman M P. Cell membrane microparticles in blood and blood products: potentially pathogenic agents and diagnostic markers.  Transfus Med Rev. 2006;  20 1-26
  • 59 Sierko E, Wojtukiewicz M Z. Platelets and angiogenesis in malignancy.  Semin Thromb Hemost. 2004;  30 95-108
  • 60 Bruland O S, Hoifodt H, Saeter G, Smeland S, Fodstad O. Hematogenous micrometastases in osteosarcoma patients.  Clin Cancer Res. 2005;  11 4666-4673
  • 61 Kim H K, Song K S, Chung J H, Lee K R, Lee S N. Platelet microparticles induce angiogenesis in vitro.  Br J Haematol. 2004;  124 376-384
  • 62 Mostefai H A, Andriantsitohaina R, Martinez M C. Plasma membrane microparticles in angiogenesis: role in ischemic diseases and in cancer.  Physiol Res. 2008;  57 311-320
  • 63 Yang C, Mwaikambo B R, 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-R476
  • 64 Kim H K, Song K S, Park Y S, Kim C M, Lee K R. Method comparison of flow cytometric assay of platelet microparticles and changes of platelet microparticles during cancer chemotherapy.  Thromb Haemost. 2002;  87 547-548
  • 65 Pihusch R, Hohnberg B, Salat C, Pihusch M, Hiller E, Kolb H J. Platelet flow cytometric findings in patients undergoing conditioning therapy for allogeneic hematopoietic stem cell transplantation.  Ann Hematol. 2002;  81 454-461
  • 66 Tesselaar M E, Romijn F P, Van Der Linden I K, Prins F A, Bertina R M, Osanto S. Microparticle-associated tissue factor activity: a link between cancer and thrombosis?.  J Thromb Haemost. 2007;  5 520-527
  • 67 Zwicker J I, Furie B C, Furie B. Cancer-associated thrombosis.  Crit Rev Oncol Hematol. 2007;  62 126-136
  • 68 Furie B, Furie B C. Cancer-associated thrombosis.  Blood Cells Mol Dis. 2006;  36 177-181
  • 69 Zwaal R F, Comfurius P, Bevers E M. Scott syndrome, a bleeding disorder caused by defective scrambling of membrane phospholipids.  Biochim Biophys Acta. 2004;  1636 119-128
  • 70 Solum N O. Procoagulant expression in platelets and defects leading to clinical disorders.  Arterioscler Thromb Vasc Biol. 1999;  19 2841-2846
  • 71 Faure V, Dou L, Sabatier F et al.. Elevation of circulating endothelial microparticles in patients with chronic renal failure.  J Thromb Haemost. 2006;  4 566-573
  • 72 Ogata N, Nomura S, Shouzu A, Imaizumi M, Arichi M, Matsumura M. Elevation of monocyte-derived microparticles in patients with diabetic retinopathy.  Diabetes Res Clin Pract. 2006;  73 241-248
  • 73 Ogata N, Imaizumi M, Nomura S et al.. Increased levels of platelet-derived microparticles in patients with diabetic retinopathy.  Diabetes Res Clin Pract. 2005;  68 193-201
  • 74 Omoto S, Nomura S, Shouzu A, Nishikawa M, Fukuhara S, Iwasaka T. Detection of monocyte-derived microparticles in patients with type II diabetes mellitus.  Diabetologia. 2002;  45 550-555
  • 75 Kline J A, Courtney D M, Kabrhel C et al.. Prospective multicenter evaluation of the pulmonary embolism rule-out criteria.  J Thromb Haemost. 2008;  6 772-780
  • 76 Wolf S J, McCubbin T R, Nordenholz K E, Naviaux N W, Haukoos J S. Assessment of the pulmonary embolism rule-out criteria rule for evaluation of suspected pulmonary embolism in the emergency department.  Am J Emerg Med. 2008;  26 181-185
  • 77 Furie B, Furie B C. Role of platelet P-selectin and microparticle PSGL-1 in thrombus formation.  Trends Mol Med. 2004;  10 171-178
  • 78 Newman P JBM, Griffin J, Vague I J, Preissner K T. Minutes of Working Group in Vascular Biology. Available at: http://wwwmeduncedu/isth/ssc Accessed July 15, 2008
  • 79 Enjeti A K, Lincz L F, Seldon M. Detection and measurement of microparticles: an evolving research tool for vascular biology.  Semin Thromb Hemost. 2007;  33 771-779
  • 80 Jy W, Hirstman L L, Jimenez J J. Measuring cell derived microparticles.  J Thromb Haemost. 2004;  2 1842-1851
  • 81 Freyssinet J M, Dignat-George F. More on: measuring circulating cell-derived microparticles.  J Thromb Haemost. 2005;  3 613-614
  • 82 Capitanio M, Normanno D, Pavone F S. High-precision measurements of light-induced torque on absorbing microspheres.  Opt Lett. 2004;  29 2231-2233
  • 83 Shapiro H M. Multiparameter flow cytometry of bacteria: implications for diagnostics and therapeutics.  Cytometry. 2001;  43 223-226
  • 84 Shapiro H M. Multistation multiparameter flow cytometry: a critical review and rationale.  Cytometry. 1983;  3 227-243
  • 85 Enjeti A K, Seldon M. Biomaleimide as a generic stain for detection and quantitation of microparticles.  Int J Lab Haematol. 2007 July;  , [Epub ahead of publication]
  • 86 Exner T, Joseph J, Low J, Connor D, Ma D. A new activated factor X-based clotting method with improved specificity for procoagulant phospholipid.  Blood Coagul Fibrinolysis. 2003;  14 773-779
  • 87 Empson M B. Statistics in the pathology laboratory: diagnostic test interpretation.  Pathology. 2002;  34 365-369
  • 88 Empson M B. Statistics in the pathology laboratory: characteristics of diagnostic tests.  Pathology. 2001;  33 93-95

Anoop K EnjetiM.B.B.S. M.D. F.R.C.P.A. 

Department of Haematology level 4, Hunter Haematology Research Group, New Medical Building, Calvary Mater Hospital

Waratah Newcastle 2298, Australia

Email: Anoop.Enjeti@mater.health.nsw.gov.au

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