Die Rolle von Thrombozyten bei Hämostase, Thrombose, Immunabwehr und Entzündung

 

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Zusammenfassung

Unsere Vorstellung über die verschiedenen Rollen der Thrombozyten hat sich in den letzten Jahren deutlich verändert. Waren Thrombozyten bis vor wenigen Jahren den meisten nur als Akteure bei der primären Hämostase und als Lieferant für eine negativ geladene Phospholipidoberfläche bekannt, so musste dieses Bild spätestens mit der Entdeckung von spezifischen Proteinrezeptoren für Gerinnungsfaktoren auf der Plättchenoberfläche revidiert werden. Neben ihrer regulativen Rolle in der Hämostase können Thrombozyten auch als Abwehrzellen angesehen werden. Als solche interagieren sie direkt mit Mikroorganismen, wie Bakterien, pathogenen Pilzen und Protozoen. In Wechselwirkung mit Endothelzellen und Leukozyten nehmen sie direkten Einfluss auf unspezifische und spezifische Abwehr. Thrombozyten spielen zweifelsfrei eine wesentliche Rolle bei thromboembolischen Komplikationen der fortgeschrittenen arteriosklerotischen Läsion, sind aber auch schon an der initialen Entstehung der Arteriosklerose beteiligt und spielen eine wichtige Rolle bei dem Fortschreiten der Erkrankung.

Summary

The views on the role of platelets in physiology and in pathogenesis have considerably changed in the recent past. While platelets had previously been seen only as contributors in primary haemostasis and as donors of negatively charged phospholipids to support thrombin formation, this view has had to be revised, at least since the discovery of specific receptors for coagulation factors on the platelet surface. Platelets are part of the body's immune defence system. They can interact with bacteria, pathogenic fungi and protozoa. The interaction of platelets with endothelial cells and leukocytes is crucial in innate and adaptive immunity. Platelets participate in the pathogenesis of the initial lesions and in the progression of atherrosclerosis by inducing chronic inflammatory processes at the vascular wall, which result in the development of atherosclerotic lesions and atherothrombosis.

Literatur

• 1 Baglia F A, Shrimpton C N, Emsley J. et al . Factor XI interacts with the leucine-rich repeats of glycoprotein Ibalpha on the activated platelet.  J Biol Chem. 2004;  279 49323-9
  Google Scholar
• 2 Barry O P, Pratico D, Savani R C, FitzGerald G A. Modulation of monocyte-endothelial cell interactions by platelet microparticles.  J Clin Invest. 1998;  102 136-44
  Google Scholar
• 3 Brodde M F, Horn M, Van Aken H, Niemann S, Jurk K, Kehrel B E. Prothrombotic tendency upon inflammatory conditions - alpha defensins (HNP-1/2/3) are strong platelet agonists.  J Thromb Haemost. 2005;  3 Suppl 1 OR016
  Google Scholar
• 4 Chaipan C, Soilleux E J, Simpson P. et al . DC-SIGN and CLEC-2 mediate human immunodeficiency virus type 1 capture by platelets.  J Virol. 2006;  80 8951-60
  Google Scholar
• 5 Clemetson K J, Clemetson J M, Proudfoot A E. et al . Functional expression of CCR1, CCR3, CCR4, and CXCR4 chemokine receptors on human platelets.  Blood. 2000;  96 4046-54
  Google Scholar
• 6 Clemetson K J. A short history of platelet glycoprotein Ib complex.  Thromb Haemost. 2007;  98 63-8
  Google Scholar
• 7 Coller B S, Anderson K, Weisman H F. New antiplatelet agents: platelet GPIIb/IIIa antagonists.  Thromb Haemost. 1995;  74 302-8
  Google Scholar
• 8 Coughlin S R. Thrombin signalling and protease-activated receptors.  Nature. 2000;  407 258-64
  Google Scholar
• 9 Crombie R, Silverstein R L, MacLow C. et al . Identification of a CD36-related thrombospondin 1-binding domain in HIV-1 envelope glycoprotein gp120: relationship to HIV-1-specific inhibitory factors in human saliva.  J Exp Med. 1998;  187 25-35
  Google Scholar
• 10 Daub K, Langer H, Seizer P. et al . Platelets induce differentiation of human CD34+ progenitor cells into foam cells and endothelial cells.  FASEB J. 2006;  20 2559-61
  Google Scholar
• 11 Diacovo T G, Puri K D, Warnock R A. et al . Platelet-mediated lymphocyte delivery to high endothelial venules.  Science. 1996;  273 252-5
  Google Scholar
• 12 Dormann D, Clemetson K J, Kehrel B E. The GPIb thrombin-binding site is essential for thrombin-induced platelet procoagulant activity.  Blood. 2000;  96 2469-78
  Google Scholar
• 13 Elzey B D, Tian J, Jensen R J. et al . Platelet-mediated modulation of adaptive immunity. A communication link between innate and adaptive immune compartments.  Immunity. 2003;  19 9-19
  Google Scholar
• 14 Fitzgerald J R, Foster T J, Cox D. The interaction of bacterial pathogens with platelets.  Nat Rev Microbiol. 2006;  4 445-57
  Google Scholar
• 15 Fitzgerald J R, Loughman A, Keane F. et al . Fibronectin-binding proteins of Staphylococcus aureus mediate activation of human platelets via fibrinogen and fibronectin bridges to integrin GPIIb/IIIa and IgG binding to the FcgammaRIIa receptor.  Mol Microbiol. 2006;  59 212-30
  Google Scholar
• 16 Gawaz M. Platelets in the onset of atherosclerosis.  Blood Cells Mol Dis. 2006;  36 206-10
  Google Scholar
• 17 Jurk K, Clemetson K J, de Groot P G. et al . Thrombospondin-1 mediates platelet adhesion at high shear via glycoprotein Ib (GPIb): an alternative/backup mechanism to von Willebrand factor.  FASEB J. 2003;  17 1490-2
  Google Scholar
• 18 Jurk K, Kehrel B E. [Platelets and the new comprehension of haemostasis].  Hamostaseologie. 2005;  25 39-49
  Google Scholar
• 19 Jurk K, Strey A, Van Aken H, Janning A, Gerke V, Kehrel B E. Crosstalk between haemostasis and inflammation: Platelets modulate the adhesion and transmigration process of monocytes.  Anesth Analg. 2005;  100 Suppl S S-59
  Google Scholar
• 20 Jurk K, Kehrel B E. Inherited and acquired disorders of platelet function.  Transfus Med Hemother. 2007;  34 6-19
  Google Scholar
• 21 Jurk K, Kehrel B E. Thrombozytensekretion. In: Müller-Berghaus G und Pötsch B, editors Hämostaseologie. 2. Ausgabe. Springer Verlag Heidelberg 2008. In press
  Google Scholar
• 22 Kehrel B, Wierwille S, Clemetson K J. et al . Glycoprotein VI is a major collagen receptor for platelet activation: it recognizes the platelet-activating quaternary structure of collagen, whereas CD36, glycoprotein IIb/IIIa, and von Willebrand factor do not.  Blood. 1998;  91 491-9
  Google Scholar
• 23 Kowalska M A, Ratajczak M Z, Majka M. et al . Stromal cell-derived factor-1 and macrophage-derived chemokine: 2 chemokines that activate platelets.  Blood. 2000;  96 50-7
  Google Scholar
• 24 Lefer A M, Campbell B, Scalia R, Lefer D J. Synergism between platelets and neutrophils in provoking cardiac dysfunction after ischemia and reperfusion: role of selectins.  Circulation. 1998;  98 1322-8
  Google Scholar
• 25 Levin J. The evolution of mammalian platelets. In: Michelson AD, editor Platelets. Academic Press San Diego 2000: 3-19
  Google Scholar
• 26 Lindemann S, Tolley N D, Dixon D A. et al . Activated platelets mediate inflammatory signaling by regulated interleukin 1beta synthesis.  J Cell Biol. 2001;  154 485-90
  Google Scholar
• 27 Massberg S, Gawaz M, Gruner S. et al . A crucial role of glycoprotein VI for platelet recruitment to the injured arterial wall in vivo.  J Exp Med. 2003;  197 41-9
  Google Scholar
• 28 Massberg S, Konrad I, Schurzinger K. et al . Platelets secrete stromal cell-derived factor 1alpha and recruit bone marrow-derived progenitor cells to arterial thrombi in vivo.  J Exp Med. 2006;  203 1221-33
  Google Scholar
• 29 Niemann S, Spehr N, Van Aken H. et al . Soluble fibrin is the main mediator of Staphylococcus aureus adhesion to platelets.  Circulation. 2004;  110 193-200
  Google Scholar
• 30 Nieuwland R, Berckmans R J, Rotteveel-Eijkman R C. et al . Cell-derived microparticles generated in patients during cardiopulmonary bypass are highly procoagulant.  Circulation. 1997;  96 3534-41
  Google Scholar
• 31 O’Sullivan B P, Linden M D, Frelinger III A L. et al . Platelet activation in cystic fibrosis.  Blood. 2005;  105 4635-41
  Google Scholar
• 32 Offermanns S. Activation of platelet function through G protein-coupled receptors.  Circ Res. 2006;  99 1293-304
  Google Scholar
• 33 Peschel A. How do bacteria resist human antimicrobial peptides?.  Trends Microbiol. 2002;  10 179-86
  Google Scholar
• 34 Pitchford S C, Momi S, Giannini S. et al . Platelet P-selectin is required for pulmonary eosinophil and lymphocyte recruitment in a murine model of allergic inflammation.  Blood. 2005;  105 2074-81
  Google Scholar
• 35 Polgar J, Clemetson J M, Kehrel B E. et al . Platelet activation and signal transduction by convulxin, a C-type lectin from Crotalus durissus terrificus (tropical rattlesnake) venom via the p62/GPVI collagen receptor.  J Biol Chem. 1997;  272 13576-83
  Google Scholar
• 36 Rennemeier C, Hammerschmidt S, Niemann S. et al . Thrombospondin-1 promotes cellular adherence of gram-positive pathogens via recognition of peptidoglycan.  FASEB J. 2007;  21 3118-32
  Google Scholar
• 37 Roberts H R, Hoffman M, Monroe D M. A cell-based model of thrombin generation.  Semin Thromb Hemost. 2006;  32 Suppl 1 32-8
  Google Scholar
• 38 Ross R. Atherosclerosis - an inflammatory disease.  N Engl J Med. 1999;  340 115-26
  Google Scholar
• 39 Ruggeri Z M. Mechanisms of shear-induced platelet adhesion and aggregation.  Thromb Haemost. 1993;  70 119-23
  Google Scholar
• 40 Santoso S, Sachs U J, Kroll H. et al . The junctional adhesion molecule 3 (JAM-3) on human platelets is a counterreceptor for the leukocyte integrin Mac-1.  J Exp Med. 2002;  196 679-91
  Google Scholar
• 41 Simon D I, Chen Z, Xu H. et al . Platelet glycoprotein ibalpha is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18).  J Exp Med. 2000;  192 193-204
  Google Scholar
• 42 Sims P J, Wiedmer T, Esmon C T. 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 17049-57
  Google Scholar
• 43 Tamagawa-Mineoka R, Katoh N, Ueda E. et al . The role of platelets in leukocyte recruitment in chronic contact hypersensitivity induced by repeated elicitation.  Am J Pathol. 2007;  170 2019-29
  Google Scholar
• 44 Hundelshausen P von, Weber C. Platelets as immune cells: bridging inflammation and cardiovascular disease.  Circ Res. 2007;  100 27-40
  Google Scholar
• 45 Weyrich A S, Lindemann S, Tolley N D. et al . Change in protein phenotype without a nucleus: translational control in platelets.  Semin Thromb Hemost. 2004;  30 491-8
  Google Scholar

Prof. Dr. rer. nat. Beate E. Kehrel

Universitätsklinikum Münster, Experimentelle und Klinische Hämostaseologie, Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin

Phone: 0251/8356725

Fax: 0251/8352441

Email: kehrel@uni-muenster.de