Platelet- and Megakaryocyte-Derived Microparticles

 

 Buy Article Permissions and Reprints

ABSTRACT

Platelet microparticles are the most abundant cell-derived microparticle subtype in the circulation. Yet the mechanism by which platelet microparticles are formed is poorly defined. This review highlights the concept of the generation of microparticles from platelets and their precursor cells, megakaryocytes. Special emphasis is placed on the mechanisms of microparticle formation and novel functions for microparticles in normal physiology and disease states.

REFERENCES

• 1 Wolf P. The nature and significance of platelet products in human plasma.  Br J Haematol. 1967;  13(3) 269-288
  CrossrefPubMedGoogle Scholar
• 2 George J N, Thoi L L, McManus L M, Reimann T A. Isolation of human platelet membrane microparticles from plasma and serum.  Blood. 1982;  60(4) 834-840
  PubMedGoogle Scholar
• 3 George J N, Pickett E B, Saucerman S et al. Platelet surface glycoproteins. Studies on resting and activated platelets and platelet membrane microparticles in normal subjects, and observations in patients during adult respiratory distress syndrome and cardiac surgery.  J Clin Invest. 1986;  78(2) 340-348
  CrossrefPubMedGoogle Scholar
• 4 Horstman L L, Ahn Y S. Platelet microparticles: a wide-angle perspective.  Crit Rev Oncol Hematol. 1999;  30(2) 111-142
  CrossrefPubMedGoogle Scholar
• 5 Joop K, Berckmans R J, Nieuwland R et al. Microparticles from patients with multiple organ dysfunction syndrome and sepsis support coagulation through multiple mechanisms.  Thromb Haemost. 2001;  85(5) 810-820
  PubMedGoogle Scholar
• 6 Berckmans R J, Neiuwland R, Böing A N, Romijn F P, Hack C E, Sturk A. Cell-derived microparticles circulate in healthy humans and support low grade thrombin generation.  Thromb Haemost. 2001;  85(4) 639-646
  PubMedGoogle Scholar
• 7 Heijnen H F, Schiel A E, Fijnheer R, Geuze H J, Sixma J J. 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(11) 3791-3799
  PubMedGoogle Scholar
• 8 Flaumenhaft R. Formation and fate of platelet microparticles.  Blood Cells Mol Dis. 2006;  36(2) 182-187
  CrossrefPubMedGoogle Scholar
• 9 Rand M L, Wang H, Bang K W, Packham M A, Freedman J. Rapid clearance of procoagulant platelet-derived microparticles from the circulation of rabbits.  J Thromb Haemost. 2006;  4(7) 1621-1623
  CrossrefPubMedGoogle Scholar
• 10 Bode A P, Orton S M, Frye M J, Udis B J. Vesiculation of platelets during in vitro aging.  Blood. 1991;  77(4) 887-895
  PubMedGoogle Scholar
• 11 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(9) 3456-3464
  PubMedGoogle Scholar
• 12 Chow T W, Hellums J D, Thiagarajan P. Thrombin receptor activating peptide (SFLLRN) potentiates shear-induced platelet microvesiculation.  J Lab Clin Med. 2000;  135(1) 66-72
  CrossrefPubMedGoogle Scholar
• 13 Wiedmer T, Shattil S J, Cunningham M, Sims P J. 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(3) 623-632
  CrossrefPubMedGoogle Scholar
• 14 Shcherbina A, Remold-O'Donnell E. Role of caspase in a subset of human platelet activation responses.  Blood. 1999;  93(12) 4222-4231
  PubMedGoogle Scholar
• 15 Dale G L, Friese P. Bax activators potentiate coated-platelet formation.  J Thromb Haemost. 2006;  4(12) 2664-2669
  CrossrefPubMedGoogle Scholar
• 16 Bevers E M, Comfurius P, Zwaal R F. Changes in membrane phospholipid distribution during platelet activation.  Biochim Biophys Acta. 1983;  736(1) 57-66
  CrossrefPubMedGoogle Scholar
• 17 Zwaal R F, Comfurius P, Bevers E M. Surface exposure of phosphatidylserine in pathological cells.  Cell Mol Life Sci. 2005;  62(9) 971-988
  CrossrefPubMedGoogle Scholar
• 18 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(2-3) 119-128
  CrossrefPubMedGoogle Scholar
• 19 Zhou Q, Zhao J, Wiedmer T, Sims P J. Normal hemostasis but defective hematopoietic response to growth factors in mice deficient in phospholipid scramblase 1.  Blood. 2002;  99(11) 4030-4038
  CrossrefPubMedGoogle Scholar
• 20 Wiedmer T, Zhao J, Li L et al. Adiposity, dyslipidemia, and insulin resistance in mice with targeted deletion of phospholipid scramblase 3 (PLSCR3).  Proc Natl Acad Sci U S A. 2004;  101(36) 13296-13301
  CrossrefPubMedGoogle Scholar
• 21 Manno S, Takakuwa Y, Mohandas N. Identification of a functional role for lipid asymmetry in biological membranes: phosphatidylserine-skeletal protein interactions modulate membrane stability.  Proc Natl Acad Sci U S A. 2002;  99(4) 1943-1948
  CrossrefPubMedGoogle Scholar
• 22 MacDonald R I. Temperature and ionic effects on the interaction of erythroid spectrin with phosphatidylserine membranes.  Biochemistry. 1993;  32(27) 6957-6964
  CrossrefPubMedGoogle Scholar
• 23 O'Toole P J, Morrison I E, Cherry R J. Investigations of spectrin-lipid interactions using fluoresceinphosphatidylethanolamine as a membrane probe.  Biochim Biophys Acta. 2000;  1466(1–2) 39-46
  CrossrefPubMedGoogle Scholar
• 24 Niggli V, Kaufmann S, Goldmann W H, Weber T, Isenberg G. Identification of functional domains in the cytoskeletal protein talin.  Eur J Biochem. 1994;  224(3) 951-957
  CrossrefPubMedGoogle Scholar
• 25 Razmara M, Hu H, Masquelier M, Li N. Glycoprotein IIb/IIIa blockade inhibits platelet aminophospholipid exposure by potentiating translocase and attenuating scramblase activity.  Cell Mol Life Sci. 2007;  64(7–8) 999-1008
  CrossrefPubMedGoogle Scholar
• 26 Niebuhr K, Giuriato S, Pedron T et al. Conversion of PtdIns(4,5)P(2) into PtdIns(5)P by the S. flexneri effector IpgD reorganizes host cell morphology.  EMBO J. 2002;  21(19) 5069-5078
  CrossrefPubMedGoogle Scholar
• 27 Raucher D, Stauffer T, Chen W et al. Phosphatidylinositol 4,5-bisphosphate functions as a second messenger that regulates cytoskeleton-plasma membrane adhesion.  Cell. 2000;  100(2) 221-228
  CrossrefPubMedGoogle Scholar
• 28 O'Connell D J, Rozenvayn N, Flaumenhaft R. Phosphatidylinositol 4,5-bisphosphate regulates activation-induced platelet microparticle formation.  Biochemistry. 2005;  44(16) 6361-6370
  CrossrefPubMedGoogle Scholar
• 29 Wang Y, Litvinov R I, Chen X et al. Loss of PIP5KIgamma, unlike other PIP5KI isoforms, impairs the integrity of the membrane cytoskeleton in murine megakaryocytes.  J Clin Invest. 2008;  118(2) 812-819
  PubMedGoogle Scholar
• 30 Hyvönen M, Macias M J, Nilges M, Oschkinat H, Saraste M, Wilmanns M. Structure of the binding site for inositol phosphates in a PH domain.  EMBO J. 1995;  14(19) 4676-4685
  PubMedGoogle Scholar
• 31 Fukami K, Furuhashi K, Inagaki M, Endo T, Hatano S, Takenawa T. Requirement of phosphatidylinositol 4,5-bisphosphate for alpha-actinin function.  Nature. 1992;  359(6391) 150-152
  CrossrefPubMedGoogle Scholar
• 32 Tsukita S, Yonemura S. Cortical actin organization: lessons from ERM (ezrin/radixin/moesin) proteins.  J Biol Chem. 1999;  274(49) 34507-34510
  CrossrefPubMedGoogle Scholar
• 33 Glantz S B, Cianci C D, Iyer R, Pradhan D, Wang K K, Morrow J S. Sequential degradation of alphaII and betaII spectrin by calpain in glutamate or maitotoxin-stimulated cells.  Biochemistry. 2007;  46(2) 502-513
  CrossrefPubMedGoogle Scholar
• 34 Fox J E, Austin C D, Boyles J K, Steffen P K. Role of the membrane skeleton in preventing the shedding of procoagulant-rich microvesicles from the platelet plasma membrane.  J Cell Biol. 1990;  111(2) 483-493
  CrossrefPubMedGoogle Scholar
• 35 Fox J E, Austin C D, Reynolds C C, Steffen P K. 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(20) 13289-13295
  PubMedGoogle Scholar
• 36 Leitinger B, McDowall A, Stanley P, Hogg N. The regulation of integrin function by Ca(2+).  Biochim Biophys Acta. 2000;  1498(2–3) 91-98
  CrossrefPubMedGoogle Scholar
• 37 Bassé F, Gaffet P, Bienvenüe 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(2) 217-224
  CrossrefPubMedGoogle Scholar
• 38 Cauwenberghs S, Feijge M A, Harper A G, Sage S O, Curvers J, Heemskerk J W. Shedding of procoagulant microparticles from unstimulated platelets by integrin-mediated destabilization of actin cytoskeleton.  FEBS Lett. 2006;  580(22) 5313-5320
  CrossrefPubMedGoogle Scholar
• 39 Schoenwaelder S M, Yuan Y, Josefsson E C et al. Two distinct pathways regulate platelet phosphatidylserine exposure and procoagulant function.  Blood. 2009;  114(3) 663-666
  CrossrefPubMedGoogle Scholar
• 40 Cohen Z, Davis-Gorman G, McDonagh P F, Ritter L. Caspase inhibition of platelet activation.  Blood Coagul Fibrinolysis. 2008;  19(4) 305-309
  CrossrefPubMedGoogle Scholar
• 41 Mason K D, Carpinelli M R, Fletcher J I et al. Programmed anuclear cell death delimits platelet life span.  Cell. 2007;  128(6) 1173-1186
  CrossrefPubMedGoogle Scholar
• 42 Dasgupta S K, Abdel-Monem H, Niravath P et al. Lactadherin and clearance of platelet-derived microvesicles.  Blood. 2009;  113(6) 1332-1339
  CrossrefPubMedGoogle Scholar
• 43 Cramer E M, Norol F, Guichard J et al. Ultrastructure of platelet formation by human megakaryocytes cultured with the Mpl ligand.  Blood. 1997;  89(7) 2336-2346
  PubMedGoogle Scholar
• 44 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(1) 33-42
  CrossrefPubMedGoogle Scholar
• 45 Flaumenhaft R, Dilks J R, Richardson J et al. Megakaryocyte-derived microparticles: direct visualization and distinction from platelet-derived microparticles.  Blood. 2009;  113(5) 1112-1121
  CrossrefPubMedGoogle Scholar
• 46 van der Zee P M, Biró E, Kó Y et al. P-selectin- and CD63-exposing platelet microparticles reflect platelet activation in peripheral arterial disease and myocardial infarction.  Clin Chem. 2006;  52(4) 657-664
  CrossrefPubMedGoogle Scholar
• 47 Cunningham C C. Actin polymerization and intracellular solvent flow in cell surface blebbing.  J Cell Biol. 1995;  129(6) 1589-1599
  CrossrefPubMedGoogle Scholar
• 48 Charras G T, Hu C K, Coughlin M, Mitchison T J. Reassembly of contractile actin cortex in cell blebs.  J Cell Biol. 2006;  175(3) 477-490
  CrossrefPubMedGoogle Scholar
• 49 Fackler O T, Grosse R. Cell motility through plasma membrane blebbing.  J Cell Biol. 2008;  181(6) 879-884
  CrossrefPubMedGoogle Scholar
• 50 Ratajczak J, Wysoczynski M, Hayek F, Janowska-Wieczorek A, Ratajczak M Z. Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication.  Leukemia. 2006;  20(9) 1487-1495
  CrossrefPubMedGoogle Scholar
• 51 Baj-Krzyworzeka M, Majka M, Pratico D et al. Platelet-derived microparticles stimulate proliferation, survival, adhesion, and chemotaxis of hematopoietic cells.  Exp Hematol. 2002;  30(5) 450-459
  CrossrefPubMedGoogle Scholar
• 52 Morel O, Toti F, Hugel B, Freyssinet J M. Cellular microparticles: a disseminated storage pool of bioactive vascular effectors.  Curr Opin Hematol. 2004;  11(3) 156-164
  CrossrefPubMedGoogle Scholar
• 53 Mack M, Kleinschmidt A, Brühl 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(7) 769-775
  CrossrefPubMedGoogle Scholar
• 54 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(10) 3143-3149
  CrossrefPubMedGoogle Scholar
• 55 Barry O P, Pratico D, Lawson J A, FitzGerald G A. Transcellular activation of platelets and endothelial cells by bioactive lipids in platelet microparticles.  J Clin Invest. 1997;  99(9) 2118-2127
  CrossrefPubMedGoogle Scholar
• 56 Barry O P, Praticò D, Savani R C, FitzGerald G A. Modulation of monocyte-endothelial cell interactions by platelet microparticles.  J Clin Invest. 1998;  102(1) 136-144
  CrossrefPubMedGoogle Scholar
• 57 Raposo G, Nijman H W, Stoorvogel W et al. B lymphocytes secrete antigen-presenting vesicles.  J Exp Med. 1996;  183(3) 1161-1172
  CrossrefPubMedGoogle Scholar
• 58 Denzer K, van Eijk M, Kleijmeer M J, Jakobson E, de Groot C, Geuze H J. Follicular dendritic cells carry MHC class II-expressing microvesicles at their surface.  J Immunol. 2000;  165(3) 1259-1265
  PubMedGoogle Scholar
• 59 Clayton A, Turkes A, Dewitt S, Steadman R, Mason M D, Hallett M B. Adhesion and signaling by B cell-derived exosomes: the role of integrins.  FASEB J. 2004;  18(9) 977-979
  PubMedGoogle Scholar
• 60 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(5) 847-856
  CrossrefPubMedGoogle Scholar
• 61 Deregibus M C, 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(7) 2440-2448
  CrossrefPubMedGoogle Scholar
• 62 Hunter M P, Ismail N, Zhang X et al. Detection of microRNA expression in human peripheral blood microvesicles.  PLoS One. 2008;  3(11) e3694
  CrossrefPubMedGoogle Scholar

Robert FlaumenhaftM.D. Ph.D. 

Center for Life Sciences, Room no. 939

Beth Israel Deaconess Medical Center, 3 Blackfan Circle, Boston, MA 02215

Email: rflaumen@bidmc.harvard.edu