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Nature et signification des microparticules dans le sepsis

The nature and significance of microparticles in sepsis

  • Enseignement Supérieur en Réanimation Fondamental
  • Published:
Réanimation

Résumé

Le choc septique est caractérisé par une intense activation cellulaire inflammatoire, à l’origine d’un remodelage de la membrane aboutissant à la libération de microparticules. Les microparticules constituent une réserve de bioeffecteurs qui modulent de nombreuses fonctions vasculaires. Au cours du choc septique, l’interaction hôte-pathogène peut être responsable de la génération de microparticules procoagulantes d’origine endothéliale, plaquettaire, érythrocytaire ou granulocytaire, susceptibles d’activer la réponse inflammatoire, l’apoptose cellulaire et la coagulation. Certaines microparticules pourraient promouvoir l’importante dysfonction vasculaire observée au cours du choc septique, participer à la modulation du statut oxydant ou encore, participer à la génération d’un état de coagulopathie disséminée. Ce travail constitue une mise au point sur les dernières connaissances accumulées sur les propriétés biologiques des microparticules pour tenter d’identifier leur implication dans le choc septique, comme marqueur biologique ou cible thérapeutique potentielle.

Abstract

Septic shock is characterized by an increased inflammatory process and cell activation, inducing membrane remodeling and microparticles release. These microparticles represent a pool of bioactive effectors that modulate several vascular functions. During sepsis, host-pathogen interaction leads to the generation of endothelium-, platelet-, erythrocyteand granulocyte-derived procoagulant microparticles, which could promote cellular inflammatory response, apoptosis and activate coagulation. Microparticles may also potentially participate in the arterial dysfunction characterizing septic shock, tune the oxidative status and induce procoagulant state. This review focuses on the latest knowledge accumulated on the biological properties of microparticles in order to identify their involvement in sepsis or septic shock, as a biological marker or potential therapeutic target.

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Références

  1. Parrillo JE (1993) Pathogenetic mechanisms of septic shock. N Engl J Med 328:1471–1477

    Article  PubMed  CAS  Google Scholar 

  2. Wolf P (1967) The nature and significance of platelet products in human plasma. Br J Haematol 13:269–288

    Article  PubMed  CAS  Google Scholar 

  3. Morel O, Toti F, Hugel B, Freyssinet JM (2004) Cellular microparticles: a disseminated storage pool of bioactive vascular effectors. Curr Opin Hematol 11:156–164

    Article  PubMed  CAS  Google Scholar 

  4. Tushuizen ME, Diamant M, Sturk A, Nieuwland R (2011) Cellderived microparticles in the pathogenesis of cardiovascular disease: friend or foe? Arterioscler Thromb Vasc Biol 31:4–9

    Article  PubMed  CAS  Google Scholar 

  5. Meziani F (2008) Microparticles are vectors of paradoxical information in vascular cells including the endothelium: role in health and diseases. Pharmacol Rep 60:75–84

    PubMed  CAS  Google Scholar 

  6. Berckmans RJ, Nieuwland R, Boing AN, et al (2001) Cellderived microparticles circulate in healthy humans and support low grade thrombin generation. Thromb Haemost 85:639–646

    PubMed  CAS  Google Scholar 

  7. Flaumenhaft R, Dilks JR, Richardson J, et al (2009) Megakaryocyte-derived microparticles: direct visualization and distinction from platelet-derived microparticles. Blood 113:1112–1121

    Article  PubMed  CAS  Google Scholar 

  8. Mallat Z, Benamer H, Hugel B, et al (2000) Elevated levels of shed membrane microparticles with procoagulant potential in the peripheral circulating blood of patients with acute coronary syndromes. Circulation 101:841–843

    Article  PubMed  CAS  Google Scholar 

  9. VanWijk MJ, Nieuwland R, Boer K, et al (2002) Microparticle subpopulations are increased in preeclampsia: possible involvement in vascular dysfunction? Am J Obstet Gynecol 187:450–456

    Article  PubMed  Google Scholar 

  10. Nieuwland R, Berckmans RJ, McGregor S, et al (2000) Cellular origin and procoagulant properties of microparticles in meningococcal sepsis. Blood 95:930–935

    PubMed  CAS  Google Scholar 

  11. Sabatier F, Darmon P, Hugel B, et al (2002) Type 1 and type 2 diabetic patients display different patterns of cellular microparticles. Diabetes 51:2840–2845

    Article  PubMed  CAS  Google Scholar 

  12. Leroyer AS, Tedgui A, Boulanger CM (2008) Role of microparticles in atherothrombosis. J Intern Med 263:528–537

    Article  PubMed  CAS  Google Scholar 

  13. Mortaza S, Martinez MC, Baron-Menguy C, et al (2009) Detrimental hemodynamic and inflammatory effects of microparticles originating from septic rats. Crit Care Med 37:2045–2050

    Article  PubMed  CAS  Google Scholar 

  14. Freyssinet JM (2003) Cellular microparticles: what are they bad or good for? J Thromb Haemost 1:1655–1662

    Article  PubMed  CAS  Google Scholar 

  15. Zwaal RF, Schroit AJ (1997) Pathophysiologic implications of membrane phospholipid asymmetry in blood cells. Blood 89:1121–1132

    PubMed  CAS  Google Scholar 

  16. Baj-Krzyworzeka M, Majka M, Pratico D, et al (2002) Plateletderived microparticles stimulate proliferation, survival, adhesion, and chemotaxis of hematopoietic cells. Exp Hematol 30:450–459

    Article  PubMed  CAS  Google Scholar 

  17. Rauch U, Bonderman D, Bohrmann B, et al (2000) Transfer of tissue factor from leukocytes to platelets is mediated by CD15 and tissue factor. Blood 96:170–175

    PubMed  CAS  Google Scholar 

  18. Scholz T, Temmler U, Krause S, et al (2002) Transfer of tissue factor from platelets to monocytes: role of platelet-derived microvesicles and CD62P. Thromb Haemost 88:1033–1038

    PubMed  CAS  Google Scholar 

  19. Mause SF, Weber C (2010) Microparticles: protagonists of a novel communication network for intercellular information exchange. Circ Res 107:1047–1057

    Article  PubMed  CAS  Google Scholar 

  20. Morel O, Ohlmann P, Epailly E, et al (2008) Endothelial cell activation contributes to the release of procoagulant microparticles during acute cardiac allograft rejection. J Heart Lung Transplant 27:38–45

    Article  PubMed  Google Scholar 

  21. Satta N, Freyssinet JM, Toti F (1997) The significance of human monocyte thrombomodulin during membrane vesiculation and after stimulation by lipopolysaccharide. Br J Haematol 96:534–542

    Article  PubMed  CAS  Google Scholar 

  22. Thery C, Zitvogel L, Amigorena S (2002) Exosomes: composition, biogenesis and function. Nat Rev Immunol 2:569–579

    PubMed  CAS  Google Scholar 

  23. Morel O, Jesel L, Freyssinet JM, Toti F (2011) Cellular mechanisms underlying the formation of circulating microparticles. Arterioscler Thromb Vasc Biol 31:15–26

    Article  PubMed  CAS  Google Scholar 

  24. Guha M, Mackman N (2001) LPS induction of gene expression in human monocytes. Cell Signal 13:85–94

    Article  PubMed  CAS  Google Scholar 

  25. Mesri M, Altieri DC (1999) Leukocyte microparticles stimulate endothelial cell cytokine release and tissue factor induction in a JNK1 signaling pathway. J Biol Chem 274:23111–23118

    Article  PubMed  CAS  Google Scholar 

  26. Dubyak GR (2012) P2X7 receptor regulation of non-classical secretion from immune effector cells. Cell Microbiol 14:1697–1706

    Article  PubMed  CAS  Google Scholar 

  27. Chiao CW, Tostes RC, Webb RC (2008) P2X7 receptor activation amplifies lipopolysaccharide-induced vascular hyporeactivity via interleukin-1 beta release. J Pharmacol Exp Ther 326:864–870

    Article  PubMed  CAS  Google Scholar 

  28. MacKenzie A, Wilson HL, Kiss-Toth E, et al (2001) Rapid secretion of interleukin-1beta by microvesicle shedding. Immunity 15:825–835

    Article  PubMed  CAS  Google Scholar 

  29. Wang J-G, Williams JC, Davis BK, et al (2011) Monocytic microparticles activate endothelial cells in an IL-1β-dependent manner. Blood 118:2366–2374

    Article  PubMed  CAS  Google Scholar 

  30. Qu Y, Dubyak GR (2009) P2X7 receptors regulate multiple types of membrane trafficking responses and non-classical secretion pathways. Purinergic Signal 5:163–173

    Article  PubMed  CAS  Google Scholar 

  31. Brown GT, McIntyre TM (2011) Lipopolysaccharide signaling without a nucleus: kinase cascades stimulate platelet shedding of proinflammatory IL-1β-rich microparticles. J Immunol 186:5489–5496

    Article  PubMed  CAS  Google Scholar 

  32. Furlan-Freguia C, Marchese P, Gruber A, et al (2011) P2X7 receptor signaling contributes to tissue factor-dependent thrombosis in mice. J Clin Invest 121:2932–2944

    Article  PubMed  CAS  Google Scholar 

  33. Chironi GN, Simon A, Boulanger CM, et al (2010) Circulating microparticles may influence early carotid artery remodeling. J Hypertens 28:789–796

    Article  PubMed  CAS  Google Scholar 

  34. Densmore JC, Signorino PR, Ou J, et al (2006) Endotheliumderived microparticles induce endothelial dysfunction and acute lung injury. Shock 26:464–471

    Article  PubMed  CAS  Google Scholar 

  35. Boulanger CM, Scoazec A, Ebrahimian T, et al (2001) Circulating microparticles from patients with myocardial infarction cause endothelial dysfunction. Circulation 104:2649–2652

    Article  PubMed  CAS  Google Scholar 

  36. Martin S, Tesse A, Hugel B, et al (2004) Shed membrane particles from T lymphocytes impair endothelial function and regulate endothelial protein expression. Circulation 109:1653–1659

    Article  PubMed  Google Scholar 

  37. Tesse A, Martinez MC, Hugel B, et al (2005) Upregulation of proinflammatory proteins through NF-kappaB pathway by shed membrane microparticles results in vascular hyporeactivity. Arterioscler Thromb Vasc Biol 25:2522–2527

    Article  PubMed  CAS  Google Scholar 

  38. Pfister SL (2004) Role of platelet microparticles in the production of thromboxane by rabbit pulmonary artery. Hypertension 43:428–433

    Article  PubMed  CAS  Google Scholar 

  39. Martinez MC, Tesse A, Zobairi F, Andriantsitohaina R (2005) Shed membrane microparticles from circulating and vascular cells in regulating vascular function. Am J Physiol Heart Circ Physiol 288:H1004–H1009

    Article  PubMed  CAS  Google Scholar 

  40. Meziani F, Tesse A, David E, et al (2006) Shed membrane particles from preeclamptic women generate vascular wall inflammation and blunt vascular contractility. Am J Pathol 169:1473–1483

    Article  PubMed  CAS  Google Scholar 

  41. Tesse A, Meziani F, David E, et al (2007) Microparticles from preeclamptic women induce vascular hyporeactivity in vessels from pregnant mice through an overproduction of NO. Am J Physiol Heart Circ Physiol 293:H520–H525

    Article  PubMed  CAS  Google Scholar 

  42. Amabile N, Guerin AP, Leroyer A, et al (2005) Circulating endothelial microparticles are associated with vascular dysfunction in patients with end-stage renal failure. J Am Soc Nephrol 16:3381–3388

    Article  PubMed  CAS  Google Scholar 

  43. Morel N, Morel O, Delabranche X, et al (2006) [Microparticles during sepsis and trauma. A link between inflammation and thrombotic processes]. Ann Fr Anesth Reanim 25:955–966

    Article  PubMed  CAS  Google Scholar 

  44. Barry OP, Kazanietz MG, Pratico D, FitzGerald GA (1999) Arachidonic acid in platelet microparticles up-regulates cyclooxygenase-2-dependent prostaglandin formation via a protein kinase C/mitogen-activated protein kinase-dependent pathway. J Biol Chem 274:7545–7556

    Article  PubMed  CAS  Google Scholar 

  45. Soriano AO, Jy W, Chirinos JA, et al (2005) Levels of endothelial and platelet microparticles and their interactions with leukocytes negatively correlate with organ dysfunction and predict mortality in severe sepsis. Crit Care Med 33:2540–2546

    Article  PubMed  Google Scholar 

  46. Brodsky SV, Zhang F, Nasjletti A, Goligorsky MS (2004) Endothelium-derived microparticles impair endothelial function in vitro. Am J Physiol Heart Circ Physiol 286:H1910–H1915

    Article  PubMed  CAS  Google Scholar 

  47. Janiszewski M, Do Carmo AO, Pedro MA, et al (2004) Plateletderived exosomes of septic individuals possess proapoptotic NAD(P)H oxidase activity: A novel vascular redox pathway. Crit Care Med 32:818–825

    Article  PubMed  CAS  Google Scholar 

  48. Annane D, Bellissant E, Cavaillon JM (2005) Septic shock. Lancet 365:63–78

    Article  PubMed  CAS  Google Scholar 

  49. Dhainaut JF, Charpentier J (2002) CIVD et défaillance d’organes: arguments expérimentaux et cliniques. Réanimation 11:599–607

    Article  Google Scholar 

  50. Delabranche X, Berger A, Boisramé-Helms J, Meziani F (2012) Microparticles and infectious diseases. Med Mal Infect 42:335–343

    Article  PubMed  CAS  Google Scholar 

  51. Dignat-George F, Camoin-Jau L, Sabatier F, et al (2004) Endothelial microparticles: a potential contribution to the thrombotic complications of the antiphospholipid syndrome. Thromb Haemost 91:667–673

    PubMed  CAS  Google Scholar 

  52. Morel O (2005) Les MP circulantes: rôles physiologiques dans les maladies inflammatoires et thrombotiques. Rev Med Interne 2:791–801

    Article  Google Scholar 

  53. Lane DA, Philippou H, Huntington JA (2005) Directing thrombin. Blood 106:2605–2612

    Article  PubMed  CAS  Google Scholar 

  54. Geisbert TW, Young HA, Jahrling PB, et al (2003) Mechanisms underlying coagulation abnormalities in ebola hemorrhagic fever: overexpression of tissue factor in primate monocytes/macrophages is a key event. J Infect Dis 188:1618–1629

    Article  PubMed  CAS  Google Scholar 

  55. Satta N, Toti F, Feugeas O, et al (1994) Monocyte vesiculation is a possible mechanism for dissemination of membrane-associated procoagulant activities and adhesion molecules after stimulation by lipopolysaccharide. J Immunol 153:3245–3255

    PubMed  CAS  Google Scholar 

  56. Perez-Casal M, Downey C, Fukudome K, et al (2005) Activated protein C induces the release of microparticle-associated endothelial protein C receptor. Blood 105:1515–1522

    Article  PubMed  CAS  Google Scholar 

  57. Meziani F, Delabranche X, Mortaza S, Asfar P (2008) Les microparticules circulantes: un nouvel acteur dans le sepsis ? Réanimation 17:120–125

    Article  Google Scholar 

  58. van der Meijden PEJ, van Schilfgaarde M, van Oerle R, et al (2012) Platelet- and erythrocyte-derived microparticles trigger thrombin generation via factor XIIa. J Thromb Haemost 10:1355–1312

    Article  Google Scholar 

  59. Héloire F, Weill B, Weber S, Batteux F (2003) Aggregates of endothelial microparticles and platelets circulate in peripheral blood. Variations during stable coronary disease and acute myocardial infarction. Thromb Res 110:173–180

    Google Scholar 

  60. Leroyer A (2010) Endothelial-derived microparticles: Biological conveyers at the crossroad of inflammation thrombosis and angiogenesis. Thromb Haemost 104:456–463

    Article  PubMed  CAS  Google Scholar 

  61. Distler JHW, Huber LC, Gay S, et al (2006) Microparticles as mediators of cellular cross-talk in inflammatory disease. Autoimmunity 39:683–690

    Article  PubMed  CAS  Google Scholar 

  62. Dejouvencel T, Doeuvre L, Lacroix R, et al (2010) Fibrinolytic cross-talk: a new mechanism for plasmin formation. Blood 115:2048–2056

    Article  PubMed  CAS  Google Scholar 

  63. Dalli J, Rosignoli G, Hayhoe RPG, et al (2010) CFTR Inhibition Provokes an Inflammatory Response Associated with an Imbalance of the Annexin A1 Pathway. The American Journal of Pathology 177:176–186

    Article  PubMed  CAS  Google Scholar 

  64. Morel O, Toti F, Morel N, Freyssinet JM (2009) Microparticles in endothelial cell and vascular homeostasis: are they really noxious? Haematologica 94:313–317

    PubMed  CAS  Google Scholar 

  65. Amabile N, Heiss C, Chang V, et al (2009) Increased CD62e(+) endothelial microparticle levels predict poor outcome in pulmonary hypertension patients. J Heart Lung Transplant 28:1081–1086

    Article  PubMed  Google Scholar 

  66. Amabile N, Guérin AP, Tedgui A, et al (2012) Predictive value of circulating endothelial microparticles for cardiovascular mortality in end-stage renal failure: a pilot study. Nephrol Dial Transplant 27:1873–1880

    Article  PubMed  CAS  Google Scholar 

  67. Nozaki T, Sugiyama S, Koga H, et al (2009) Significance of a multiple biomarkers strategy including endothelial dysfunction to improve risk stratification for cardiovascular events in patients at high risk for coronary heart disease. J Am Coll Cardiol 54:601–608

    Article  PubMed  Google Scholar 

  68. Sinning J-M, Losch J, Walenta K, et al (2011) Circulating CD31+/Annexin V+ microparticles correlate with cardiovascular outcomes. Eur Heart J 32:2034–2041

    Article  PubMed  CAS  Google Scholar 

  69. Jung K-H, Chu K, Lee S-T, et al (2009) Circulating endothelial microparticles as a marker of cerebrovascular disease. Ann Neurol 66:191–199

    Article  PubMed  CAS  Google Scholar 

  70. Baron M, Boulanger CM, Staels B, Tailleux A (2012) Cellderived microparticles in atherosclerosis: biomarkers and targets for pharmacological modulation? J Cell Mol Med 16:1365–1376

    Article  PubMed  CAS  Google Scholar 

  71. Sommeijer DW, Joop K, Leyte A, et al (2005) Pravastatin reduces fibrinogen receptor gpIIIa on platelet-derived microparticles in patients with type 2 diabetes. J Thromb Haemost 3:1168–1171

    Article  PubMed  CAS  Google Scholar 

  72. Mobarrez F, He S, Bröijersen A, et al (2011) Atorvastatin reduces thrombin generation and expression of tissue factor, P-selectin and GPIIIa on platelet-derived microparticles in patients with peripheral arterial occlusive disease. Thromb Haemost 106:344–352

    Article  PubMed  CAS  Google Scholar 

  73. Esposito K, Ciotola M, Giugliano D (2006) Pioglitazone reduces endothelial microparticles in the metabolic syndrome. Arterioscler Thromb Vasc Biol 26:1926

    Article  PubMed  CAS  Google Scholar 

  74. Bardelli C, Amoruso A, Federici Canova D, et al (2012) Autocrine activation of human monocyte/macrophages by monocytederived microparticles and modulation by PPARγ ligands. Br J Pharmacol 1165:716–728

    Article  PubMed  CAS  Google Scholar 

  75. Martinez MC, Tual-Chalot S, Leonetti D, Andriantsitohaina R (2011) Microparticles: targets and tools in cardiovascular disease. Trends Pharmacol Sci 32:659–665

    Article  PubMed  CAS  Google Scholar 

  76. Sennoun N, Baron-Menguy C, Burban M, et al (2009) Recombinant human activated protein C improves endotoxemia-induced endothelial dysfunction: a blood-free model in isolated mouse arteries. Am J Physiol Heart Circ Physiol 297:H277–H282

    Article  PubMed  CAS  Google Scholar 

  77. Sennoun N, Levy B (2010) Effets hémodynamiques de la protéine C activée dans le choc septique. Réanimation 19:142–145

    Article  Google Scholar 

  78. Sennoun N, Meziani F, Dessebe O, et al (2009) Activated protein C improves lipopolysaccharide-induced cardiovascular dysfunction by decreasing tissular inflammation and oxidative stress. Crit Care Med 37:246–255

    Article  PubMed  Google Scholar 

  79. Perez-Casal M, Thompson V, Downey C, et al (2011) The clinical and functional relevance of microparticles induced by activated protein C treatment in sepsis. Crit Care 15:R195

    Article  PubMed  Google Scholar 

  80. Mosnier LO, Zlokovic BV, Griffin JH (2007) The cytoprotective protein C pathway. Blood 109:3161–3172

    Article  PubMed  CAS  Google Scholar 

  81. Rautou PE, Mackman N (2012) Del-etion of microvesicles from the circulation. Circulation 125:1601–1604

    Article  PubMed  Google Scholar 

  82. Martinez MC, Andriantsitohaina R (2011) Microparticles in angiogenesis: therapeutic potential. Circ Res 109:110–119

    Article  PubMed  CAS  Google Scholar 

  83. Martínez MC, Larbret F, Zobairi F, et al (2006) Transfer of differentiation signal by membrane microvesicles harboring hedgehog morphogens. Blood 108:3012–3020

    Article  PubMed  Google Scholar 

  84. Zernecke A, Bidzhekov K, Noels H, et al (2009) Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Sci Signal 2:ra81

    Article  PubMed  Google Scholar 

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Correspondence to F. Meziani.

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Cet article correspond à la conférence faite par l’auteur au congrès de la SRLF 2013 dans la session: Voies de recherche dans le sepsis.

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Boisramé-Helms, J., Delabranche, X., Toti, F. et al. Nature et signification des microparticules dans le sepsis. Réanimation 22 (Suppl 2), 343–351 (2013). https://doi.org/10.1007/s13546-012-0537-y

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  • DOI: https://doi.org/10.1007/s13546-012-0537-y

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