Detection and Measurement of Microparticles: An Evolving Research Tool for Vascular Biology

ABSTRACT

Microparticles are small, membrane-bound vesicles that are generated from cells of different origin. It now appears that all circulating blood cells as well as endothelial cells release membranous fragments ~1 μm in size or smaller bearing at least some characteristics of the parent cell. Elevated levels of microparticles have been described in cardiovascular states, thrombotic conditions, and cancer. Various methods of detection for microparticles include flow cytometry, enzyme-linked immunoassays, and functional assays. Flow cytometry has several advantages including its ability to quantitate and identify microparticles of different cellular origin. However, the standardization of preanalytical and analytical variables for enumeration of microparticles remains a significant challenge. Newer approaches are being investigated, and an international collaboration is working on standardization of detection as well as quantitation of microparticles by flow cytometry. Although it has evolved as an important vascular biology research tool, microparticle detection needs further evaluation and refinement before it becomes truly useful as a clinical tool.

KEYWORDS

Microparticles - detection - measurement - research tool - vascular biology

REFERENCES

• 1 Freyssinet J M. Cellular microparticles: what are they bad or good for?.  J Thromb Haemost. 2003;  1 1655-1662
• 2 Ahn Y S. Cell-derived microparticles: 'miniature envoys with many faces'.  J Thromb Haemost. 2005;  3 884-887
• 3 Greenwalt T J. The how and why of exocytic vesicles.  Transfusion. 2006;  46 143-152
• 4 Jy W, Horstman L L, Arce M, Ahn Y S. Clinical significance of platelet microparticles in autoimmune thrombocytopenias.  J Lab Clin Med. 1992;  119 334-345
• 5 Stern R C, Liu K, Dodge R K, Elenitoba-Johnson K S, Layfield L J. Significance of lymphoglandular bodies in bone marrow aspiration smears.  Diagn Cytopathol. 2001;  24 240-243
• 6 Francis I M, Das D K, al-Rubah N A, Gupta S K. Lymphoglandular bodies in lymphoid lesions and non-lymphoid round cell tumours: a quantitative assessment.  Diagn Cytopathol. 1994;  11 23-27
• 7 Papadimitriou J C, Drachenberg C B, Brenner D S et al.. “Thanatosomes”: a unifying morphogenetic concept for tumor hyaline globules related to apoptosis.  Hum Pathol. 2000;  31 1455-1465
• 8 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
• 9 Kereiakes D J, Michelson A D. Platelet activation and progression to complications.  Rev Cardiovasc Med. 2006;  7 75-81
• 10 Sturk-Maquelin K N, Nieuwland R, Romijn F P et al.. Pro- and non-coagulant forms of non-cell-bound tissue factor in vivo.  J Thromb Haemost. 2003;  1 1920-1926
• 11 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
• 12 Furie B, Furie B C. Role of platelet P-selectin and microparticle PSGL-1 in thrombus formation.  Trends Mol Med. 2004;  10 171-178
• 13 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
• 14 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
• 15 Horstman L L, Jy W, Jimenez J J, Ahn Y S. Endothelial microparticles as markers of endothelial dysfunction.  Front Biosci. 2004;  9 1118-1135
• 16 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
• 17 Jy W, Mao W W, Horstman L, Tao J, Ahn Y S. Platelet microparticles bind, activate and aggregate neutrophils in vitro.  Blood Cells Mol Dis. 1995;  21 217-231 discussion 231a
• 18 Warkentin T E, Sheppard J I. Generation of platelet-derived microparticles and procoagulant activity by heparin-induced thrombocytopenia IgG/serum and other IgG platelet agonists: a comparison with standard platelet agonists.  Platelets. 1999;  10 319-326
• 19 Mackman N. Role of tissue factor in hemostasis and thrombosis.  Blood Cells Mol Dis. 2006;  36 104-107
• 20 Rauch U, Nemerson Y. Circulating tissue factor and thrombosis.  Curr Opin Hematol. 2000;  7 273-277
• 21 Raybagkar D A, Patchipulusu S, Mast A E, Hall C L. In vitro flow evaluation of recombinant tissue factor pathway inhibitor immobilized on collagen impregnated Dacron.  ASAIO J. 2004;  50 301-305
• 22 Biro E, Sturk-Maquelin K N, Vogel G M et al.. Human cell-derived microparticles promote thrombus formation in vivo in a tissue factor-dependent manner.  J Thromb Haemost. 2003;  1 2561-2568
• 23 Bogdanov V Y, Balasubramanian V, Hathcock J et al.. Alternatively spliced human tissue factor: a circulating, soluble, thrombogenic protein.  Nat Med. 2003;  9 458-462
• 24 Martinez M C, Tesse A, Zobairi F, Andriantsitohaina R. Shed membrane microparticles from circulating and vascular cells in regulating vascular function.  Am J Physiol Heart Circ Physiol. 2005;  288 H1004-H1009
• 25 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
• 26 Koga H, Sugiyama S, Kugiyama K et al.. Elevated levels of remnant lipoproteins are associated with plasma platelet microparticles in patients with type-2 diabetes mellitus without obstructive coronary artery disease.  Eur Heart J. 2006;  27 817-823
• 27 Tedgui A, Mallat Z. Apoptosis as a determinant of atherothrombosis.  Thromb Haemost. 2001;  86 420-426
• 28 Gupta A K, Hasler P, Holzgreve W, Gebhardt S, Hahn S. Induction of neutrophil extracellular DNA lattices by placental microparticles and IL-8 and their presence in preeclampsia.  Hum Immunol. 2005;  66 1146-1154
• 29 Gross P L, Furie B C, Merrill-Skoloff G, Chou J, Furie B. Leukocyte-versus microparticle-mediated tissue factor transfer during arteriolar thrombus development.  J Leukoc Biol. 2005;  78 1318-1326
• 30 Satta N, Toti F, Feugeas O et al.. Monocyte vesiculation is a possible mechanism for dissemination of membrane-associated procoagulant activities and adhesion molecules after stimulation by lipopolysaccharide.  J Immunol. 1994;  153 3245-3255
• 31 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
• 32 Ardoin S P, Shanahan J C, Pisetsky D S. The role of microparticles in inflammation and thrombosis.  Scand J Immunol. 2007;  66 159-165
• 33 White J G, Hagert K, Nipper J H, Rao G H. Functional platelets after storage in vitro for 15-21 days.  Am J Pathol. 1980;  101 613-634
• 34 Bordin J O, Heddle N M, Blajchman M A. Biologic effects of leukocytes present in transfused cellular blood products.  Blood. 1994;  84 1703-1721
• 35 Keuren J F, Magdeleyns E J, Govers-Riemslag J W, Lindhout T, Curvers J. Effects of storage-induced platelet microparticles on the initiation and propagation phase of blood coagulation.  Br J Haematol. 2006;  134 307-313
• 36 Simmons E, MaGuire C, Lichti E, Helvey W, Almond C. A comparison of the microparticles produced when two disposable-bag oxygenators and a disc oxygenator are used for cardiopulmonary bypass.  J Thorac Cardiovasc Surg. 1972;  63 613-621
• 37 Shet A S, Aras O, Gupta K et al.. Sickle blood contains tissue factor-positive microparticles derived from endothelial cells and monocytes.  Blood. 2003;  102 2678-2683
• 38 Prasad K S, Andre P, He M et al.. Soluble CD40 ligand induces beta3 integrin tyrosine phosphorylation and triggers platelet activation by outside-in signaling.  Proc Natl Acad Sci USA. 2003;  100 12367-12371
• 39 Gachet C, Ennamany R, Kretz O et al.. Bolesatine induces agglutination of rat platelets and human erythrocytes and platelets in vitro.  Hum Exp Toxicol. 1996;  15 26-29
• 40 Faye R S, Aamdal S, Hoifodt H K et al.. Immunomagnetic detection and clinical significance of micrometastatic tumor cells in malignant melanoma patients.  Clin Cancer Res. 2004;  10 4134-4139
• 41 Bruland O S, Hoifodt H, Saeter G, Smeland S, Fodstad O. Hematogenous micrometastases in osteosarcoma patients.  Clin Cancer Res. 2005;  11 4666-4673
• 42 Fondu P. Heparin-associated thrombocytopenia: an update.  Acta Clin Belg. 1995;  50 343-357
• 43 Keng T B, Chong B H. Heparin-induced thrombocytopenia and thrombosis syndrome: in vivo cross-reactivity with danaparoid and successful treatment with r-Hirudin.  Br J Haematol. 2001;  114 394-396
• 44 Nomura S, Yanabu M, Kido H et al.. Antiplatelet autoantibody-related microparticles in patients with idiopathic (autoimmune) thrombocytopenic purpura.  Ann Hematol. 1991;  62 103-107
• 45 Dachary-Prigent J, Toti F, Satta N et al.. Physiopathological significance of catalytic phospholipids in the generation of thrombin.  Semin Thromb Hemost. 1996;  22 157-164
• 46 Lopez M S, Mecerreyes D, Lopez-Cabarcos E, Lopez-Ruiz B. Amperometric glucose biosensor based on polymerized ionic liquid microparticles.  Biosens Bioelectron. 2006;  21 2320-2328
• 47 Leach J K, O'Rear E A, Patterson E, Miao Y, Johnson A E. Accelerated thrombolysis in a rabbit model of carotid artery thrombosis with liposome-encapsulated and microencapsulated streptokinase.  Thromb Haemost. 2003;  90 64-70
• 48 Jiao Y Y, Ubrich N, Hoffart V et al.. Preparation and characterization of heparin-loaded polymeric microparticles.  Drug Dev Ind Pharm. 2002;  28 1033-1041
• 49 Rodriguez M, Antunez J A, Taboada C, Seijo B, Torres D. Colon-specific delivery of budesonide from microencapsulated cellulosic cores: evaluation of the efficacy against colonic inflammation in rats.  J Pharm Pharmacol. 2001;  53 1207-1215
• 50 Tamilvanan S, Sa B. In vitro and in vivo evaluation of single-unit commercial conventional tablet and sustained-release capsules compared with multiple-unit polystyrene microparticle dosage forms of Ibuprofen.  AAPS PharmSciTech. 2006;  7 72
• 51 Vordermeier H M, Coombes A G, Jenkins P et al.. Synthetic delivery system for tuberculosis vaccines: immunological evaluation of the M. tuberculosis 38 kDa protein entrapped in biodegradable PLG microparticles.  Vaccine. 1995;  13 1576-1582
• 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 Freyssinet J M, Dignat-George F. More on: measuring circulating cell-derived microparticles.  J Thromb Haemost. 2005;  3 613-614
• 54 Jimenez J J, Jy W, Mauro L M, Horstman L L, Ahn Y S. 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
• 55 Nomura S. Function and clinical significance of platelet-derived microparticles.  Int J Hematol. 2001;  74 397-404
• 56 Enjeti A K, Lisa L, Seldon M. BioMaleimide as a generic stain for detection and quantitation of microparticles.  Int J Lab Haematol. 2007 July;  , [epub ahead of print]
• 57 Dale G L, Remenyi G, Friese P. Quantitation of microparticles released from coated-platelets.  J Thromb Haemost. 2005;  3 2081-2088
• 58 Hughes M, Hayward C P, Warkentin T E et al.. Morphological analysis of microparticle generation in heparin-induced thrombocytopenia.  Blood. 2000;  96 188-194
• 59 Jy W, Horstman L L, Jimenez J J et al.. Measuring circulating cell-derived microparticles.  J Thromb Haemost. 2004;  2 1842-1851
• 60 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
• 61 Combes V, Dignat-George F, Mutin M, Sampol J. A new flow cytometry method of platelet-derived microvesicle quantitation in plasma.  Thromb Haemost. 1997;  77 220
• 62 Enjeti A K, Lisa L, Seldon M. Preanalytical variables in the flow cytometric analysis of microparticles.  J Thromb Haemost. 2007;  5(Suppl 2) P-S-522
• 63 Kim H K, Song K S, Lee E S et al.. Optimized flow cytometric assay for the measurement of platelet microparticles in plasma: pre-analytic and analytic considerations.  Blood Coagul Fibrinolysis. 2002;  13 393-397
• 64 Robert S, Poncelet P, Camoin L, Dignat-Georges F. Standardization of microparticle counting using flow cytometry: new options and tools for the control of critical instrument settings.  J Thromb Haemost. 2007;  5(Suppl 2) P-M-442
• 65 Furie B, Furie B C. Cancer-associated thrombosis.  Blood Cells Mol Dis. 2006;  36 177-181
• 66 Morel O, Toti F, Hugel B, Freyssinet J M. Cellular microparticles: a disseminated storage pool of bioactive vascular effectors.  Curr Opin Hematol. 2004;  11 156-164
• 67 Stevens P W, Kelso D M. Imaging and analysis of immobilized particle arrays.  Anal Chem. 2003;  75 1147-1154
• 68 Banfi C, Brioschi M, Wait R et al.. Proteome of endothelial cell-derived procoagulant microparticles.  Proteomics. 2005;  5 4443-4455