RSS-Feed abonnieren
DOI: 10.1160/TH14-02-0146
Immune functions of platelets
Publikationsverlauf
Received:
17. Februar 2014
Accepted after major revision:
03. September 2014
Publikationsdatum:
04. Dezember 2017 (online)
Summary
This review collects evidence about immune and inflammatory functions of platelets from a clinician’s point of view. A focus on clinically relevant immune functions aims at stimulating further research, because the complexity of platelet immunity is incompletely understood and not yet translated into patient care. Platelets promote chronic inflammatory reactions (e.g. in atherosclerosis), modulate acute inflammatory disorders such as sepsis and other infections (participating in the host defense against pathogens), and contribute to exacerbations of autoimmune conditions (like asthma or arthritis). It would hence be obsolete to restrict a description of platelet functions to thrombosis and haemostasis – platelets clearly are the most abundant cells with immune functions in the circulation.
-
References
- 1 Davi G, Patrono C. Platelet activation and atherothrombosis. N Engl J Med 2007; 357: 2482-2494.
- 2 von Bruhl ML. et al. Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo. J Exp Med 2012; 209: 819-835.
- 3 Becattini C. et al. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med 2012; 366: 1959-1967.
- 4 Nurden AT. Platelets, inflammation and tissue regeneration. Thromb Haemost 2011; 105 (Suppl. 01) S13-33.
- 5 Bergmeier W, Wagner DD. Inflammation. In: Platelets. 2 ed.. Elsevier; 2007. pp. 713-726.
- 6 Semple JW. et al. Platelets and the immune continuum. Nat Rev Immunol 2011; 11: 264-274.
- 7 von Hundelshausen P, Weber C. Platelets as immune cells: bridging inflammation and cardiovascular disease. Circ Res 2007; 100: 27-40.
- 8 Timmons S. et al. Mechanism of human platelet activation by endotoxic glycolipid-bearing mutant Re595 of Salmonella minnesota. Blood 1986; 68: 1015-1023.
- 9 Frenette PS. et al. Platelets roll on stimulated endothelium in vivo: an interaction mediated by endothelial P-selectin. Proc Natl Acad Sci USA 1995; 92: 7450-7454.
- 10 Wagner DD, Frenette PS. The vessel wall and its interactions. Blood 2008; 111: 5271-5281.
- 11 Hui P. et al. The frequency and clinical significance of thrombocytopenia complicating critical illness: a systematic review. Chest 2011; 139: 271-278.
- 12 Forehand CC. et al. Examination of the relationship between antimicrobials and thrombocytosis. Ann Pharmacother 2012; 46: 1425-1429.
- 13 McMorran BJ. et al. Platelets kill intraerythrocytic malarial parasites and mediate survival to infection. Science 2009; 323: 797-800.
- 14 Wong CH. et al. Nucleation of platelets with blood-borne pathogens on Kupffer cells precedes other innate immunity and contributes to bacterial clearance. Nature Immunol 2013; 14: 785-792.
- 15 Manne RK. et al. Glanzmann thrombasthenia associated with human immuno-deficiency virus-positive patient. Intern J Prevent Med 2014; 5: 500-504.
- 16 Garraud O. et al. Pathogen sensing, subsequent signalling, and signalosome in human platelets. Thromb Res 2011; 127: 283-286.
- 17 Gawaz M. et al. Platelet activation and interaction with leucocytes in patients with sepsis or multiple organ failure. Eur J Clin Invest 1995; 25: 843-851.
- 18 Russwurm S. et al. Platelet and leukocyte activation correlate with the severity of septic organ dysfunction. Shock 2002; 17: 263-268.
- 19 Yaguchi A, Lobo FL, Vincent JL. et al. Platelet function in sepsis. J Thromb Haemost 2004; 2: 2096-2102.
- 20 Rondina MT. et al. The septic milieu triggers expression of spliced tissue factor mRNA in human platelets. J Thromb Haemost 2011; 9: 748-758.
- 21 Rondina MT. et al. Platelets as cellular effectors of inflammation in vascular diseases. Circ Res 2013; 112: 1506-1519.
- 22 Grabarek J. et al. Modulation of human platelet protein kinase C by endotoxic lipid A. J Clin Invest 1988; 82: 964-971.
- 23 Puram V. et al. Circulating immune complexes and platelet IgG in various diseases. Clin Exp Imunol 1984; 58: 672-676.
- 24 Cloutier N. et al. Platelets can enhance vascular permeability. Blood 2012; 120: 1334-1343.
- 25 Gresele P. et al. Altered platelet function associated with the bronchial hyperresponsiveness accompanying nocturnal asthma. J Allergy Clin Immunol 1993; 91: 894-902.
- 26 Kowal K. et al. Platelet activation in allergic asthma patients during allergen challenge with Dermatophagoides pteronyssinus. Clin Exp Allergy 2006; 36: 426-432.
- 27 Johansson MW. et al. Platelet activation, P-selectin, and eosinophil beta1-inte-grin activation in asthma. Am J Respir Crit Care Med 2012; 185: 498-507.
- 28 Pitchford SC. et al. Allergen induces the migration of platelets to lung tissue in allergic asthma. Am J Respir Crit Care Med 2008; 177: 604-612.
- 29 Pitchford SC. et al. Platelets are essential for leukocyte recruitment in allergic inflammation. J Allergy Clin Immunol 2003; 112: 109-118.
- 30 Idzko M. et al. Extracellular ATP triggers and maintains asthmatic airway inflammation by activating dendritic cells. Nat Med 2007; 13: 913-919.
- 31 Durk T. et al. Production of serotonin by tryptophan hydroxylase 1 and release via platelets contribute to allergic airway inflammation. Am J Respir Crit Care Med 2013; 187: 476-485.
- 32 McManus DD. et al. Relationship among circulating inflammatory proteins, platelet gene expression, and cardiovascular risk. Arterioscler Thromb Vasc Biol 2013; 33: 2666-2673.
- 33 Freedman JE. et al. Relation of platelet and leukocyte inflammatory transcripts to body mass index in the Framingham heart study. Circulation 2010; 122: 119-129.
- 34 Wolf D. et al. Co-Inhibitory Suppression of T Cell Activation by CD40 Protects from Obesity and Adipose Tissue Inflammation in Mice. Circulation. 2014 Epub ahead of print.
- 35 Lievens D, von Hundelshausen P. Platelets in atherosclerosis. Thromb Haemost 2011; 106: 827-838.
- 36 Gawaz M. et al. Platelets in inflammation and atherogenesis. J Clin Invest 2005; 115: 3378-3384.
- 37 Koenen RR. et al. Disrupting functional interactions between platelet chemokines inhibits atherosclerosis in hyperlipidemic mice. Nat Med 2009; 15: 97-103.
- 38 Kohler D. et al. Phosphorylation of vasodilator-stimulated phosphoprotein prevents platelet-neutrophil complex formation and dampens myocardial ischaemia-reperfusion injury. Circulation 2011; 123: 2579-2590.
- 39 Wang K. et al. Adjunctive treatment with ticagrelor, but not clopidogrel, added to tPA enables sustained coronary artery recanalisation with recovery of myocardium perfusion in a canine coronary thrombosis model. Thromb Haemost 2010; 104: 609-617.
- 40 de Groot H, Rauen U. Ischaemia-reperfusion injury: processes in pathogenetic networks: a review. Transplantation Proc 2007; 39: 481-484.
- 41 Pak S, Kondo T, Nakano Y. et al. Platelet adhesion in the sinusoid caused hepatic injury by neutrophils after hepatic ischaemia reperfusion. Platelets 2010; 21: 282-288.
- 42 Lesurtel M, Graf R, Aleil B. et al. Platelet-derived serotonin mediates liver regeneration. Science 2006; 312: 104-107.
- 43 Denis MM, Tolley ND, Bunting M. et al. Escaping the nuclear confines: signal-dependent pre-mRNA splicing in anucleate platelets. Cell 2005; 122: 379-391.
- 44 Jenne CN. et al. Platelets: bridging haemostasis, inflammation, and immunity. Intern J Lab Hematol 2013; 35: 254-261.
- 45 Zarbock A. et al. Platelet-neutrophil-interactions: linking haemostasis and inflammation. Blood Rev 2007; 21: 99-111.
- 46 Rendu F, Brohard-Bohn B. The platelet release reaction: granules’ constituents, secretion and functions. Platelets 2001; 12: 261-273.
- 47 Moore KL. et al. Identification of a specific glycoprotein ligand for P-selectin (CD62) on myeloid cells. J Cell Biol 1992; 118: 445-456.
- 48 Ruggeri ZM, Mendolicchio GL. Adhesion mechanisms in platelet function. Circ Res 2007; 100: 1673-1685.
- 49 Coller BS. et al. A murine monoclonal antibody that completely blocks the binding of fibrinogen to platelets produces a thrombasthenic-like state in normal platelets and binds to glycoproteins IIb and/or IIIa. J Clin Invest 1983; 72: 325-338.
- 50 Savage B. et al. Specific synergy of multiple substrate-receptor interactions in platelet thrombus formation under flow. Cell 1998; 94: 657-666.
- 51 Ginsberg MH. et al. Reduced surface expression and binding of fibronectin by thrombin-stimulated thrombasthenic platelets. J Clin Invest 1983; 71: 619-624.
- 52 Asch E, Podack E. Vitronectin binds to activated human platelets and plays a role in platelet aggregation. J Clin Invest 1990; 85: 1372-1378.
- 53 Wencel-Drake JD. et al. Ultrastructural localisation of human platelet thrombospondin, fibrinogen, fibronectin, and von Willebrand factor in frozen thin section. Blood 1985; 65: 929-938.
- 54 Varga-Szabo D. et al. Cell adhesion mechanisms in platelets. Arterioscler Thromb Vasc Biol 2008; 28: 403-412.
- 55 Newman PJ, Newman DK. Signal transduction pathways mediated by PECAM-1: new roles for an old molecule in platelet and vascular cell biology. Arterioscler Thromb Vasc Biol 2003; 23: 953-964.
- 56 Hayward CP. et al. Factor V is complexed with multimerin in resting platelet ly-sates and colocalizes with multimerin in platelet alpha-granules. J Biol Chem 1995; 270: 19217-19224.
- 57 Schwarz HP. et al. Identification and quantitation of protein S in human platelets. Blood 1985; 66: 1452-1455.
- 58 Hu CJ. et al. Tissue-specific expression of functional platelet factor XI is independent of plasma factor XI expression. Blood 1998; 91: 3800-3807.
- 59 Marx G. et al. Packaging zinc, fibrinogen, and factor XIII in platelet alpha-granules. J Cell Physiol 1993; 156: 437-442.
- 60 Barrientos S. et al. Growth factors and cytokines in wound healing. Wound Repair Regen 2008; 16: 585-601.
- 61 Linder BL. et al. Release of platelet-derived growth factor from human platelets by arachidonic acid. Proc Natl Acad Sci USA 1979; 76: 4107-4111.
- 62 Lo Re S. et al. Platelet-derived growth factor-producing CD4+ Foxp3+ regulatory T lymphocytes promote lung fibrosis. Am J Respir Crit Care Med 2011; 184: 1270-1281.
- 63 Fava RA. et al. Synthesis of transforming growth factor-beta 1 by megakaryocytes and its localisation to megakaryocyte and platelet alpha-granules. Blood 1990; 76: 1946-1955.
- 64 Pinzani M. et al. Effects of platelet-derived growth factor and other polypeptide mitogens on DNA synthesis and growth of cultured rat liver fat-storing cells. J Clin Invest 1989; 84: 1786-1793.
- 65 Salgado R. et al. Platelets and vascular endothelial growth factor (VEGF): a morphological and functional study. Angiogenesis 2001; 4: 37-43.
- 66 Schmaier AH. et al. Expression of platelet C1 inhibitor. Blood 1993; 82: 465-474.
- 67 Shieh BH, Travis J. The reactive site of human alpha 2-antiplasmin. J Biol Chem 1987; 262: 6055-6059.
- 68 Nylander M. et al. The role of thrombin receptors PAR1 and PAR4 for PAI-1 storage, synthesis and secretion by human platelets. Thromb Res 2012; 129: e51-58.
- 69 Brogren H. et al. Platelets synthesize large amounts of active plasminogen activator inhibitor 1. Blood 2004; 104: 3943-3948.
- 70 Kwakman PH. et al. Native thrombocidin-1 and unfolded thrombocidin-1 exert antimicrobial activity via distinct structural elements. J Biol Chem 2011; 286: 43506-43514.
- 71 George JN. et al. Immunoglobulin G is a platelet alpha granule-secreted protein. J Clin Invest 1985; 76: 2020-2025.
- 72 George JN. Platelet IgG: measurement, interpretation, and clinical significance. Progr Haemost Thromb 1991; 10: 97-126.
- 73 Falet H. et al. Platelet-associated IgAs and impaired GPVI responses in platelets lacking WIP. Blood 2009; 112: 4729-4737.
- 74 George JN, Saucerman S. Platelet IgG, IgA, IgM, and albumin: correlation of platelet and plasma concentrations in normal subjects and in patients with ITP or dysproteinemia. Blood 1988; 72: 362-365.
- 75 Berditchevski F. et al. Specific association of CD63 with the VLA-3 and VLA-6 integrins. J Biol Chem 1995; 270: 17784-17790.
- 76 Damas C. et al. The 33-kDa platelet alpha-granule membrane protein (GMP-33) is an N-terminal proteolytic fragment of thrombospondin. Thromb Haemost 2001; 86: 887-893.
- 77 Gear AR, Camerini D. Platelet chemokines and chemokine receptors: linking haemostasis, inflammation, and host defense. Microcirculation 2003; 10: 335-350.
- 78 Al-Bannawi A. et al. Chlamydia pneumoniae induces chemokine expression by platelets in patients with atherosclerosis. Medical principles and practice : international journal of the Kuwait University, Health Science Centre 2011; 20: 438-443.
- 79 Hasegawa S. et al. A comparison of FcepsilonRI-mediated RANTES release from human platelets between allergic patients and healthy individuals. Int Arch Allergy Immunol 2001; 125 (Suppl. 01) 42-47.
- 80 Antczak AJ, Singh N, Gay SR. et al. IgG-complex stimulated platelets: a source of sCD40L and RANTES in initiation of inflammatory cascade. Cell Immunol 2010; 263: 129-133.
- 81 von Hundelshausen P. et al. RANTES deposition by platelets triggers monocyte arrest on inflamed and atherosclerotic endothelium. Circulation 2001; 103: 1772-177.
- 82 Smith DF. et al. GRO family chemokines are specialized for monocyte arrest from flow. Am J Physiol Heart Circ Physiol 2005; 289: H1976-1984.
- 83 Scheuerer B. et al. The CXC-chemokine platelet factor 4 promotes monocyte survival and induces monocyte differentiation into macrophages. Blood 2000; 95: 1158-1166.
- 84 von Hundelshausen P, Koenen RR, Sack M. et al. Heterophilic interactions of platelet factor 4 and RANTES promote monocyte arrest on endothelium. Blood 2005; 105: 924-930.
- 85 Struyf S. et al. Platelets release CXCL4L1, a nonallelic variant of the chemokine platelet factor-4/CXCL4 and potent inhibitor of angiogenesis. Circ Res 2004; 95: 855-857.
- 86 Fleischer J. et al. Platelet factor 4 inhibits proliferation and cytokine release of activated human T cells. J Immunol 2002; 169: 770-777.
- 87 Mei J. et al. CXCL5 regulates chemokine scavenging and pulmonary host defense to bacterial infection. Immunity 2010; 33: 106-117.
- 88 Power CA. et al. Cloning of a full-length cDNA encoding the neutrophil-activating peptide ENA-78 from human platelets. Gene 1994; 151: 333-334.
- 89 Brandt E. et al. The beta-thromboglobulins and platelet factor 4: blood platelet-derived CXC chemokines with divergent roles in early neutrophil regulation. J Leukoc Biol 2000; 67: 471-478.
- 90 Hristov M. et al. Importance of CXC chemokine receptor 2 in the homing of human peripheral blood endothelial progenitor cells to sites of arterial injury. Circ Res 2007; 100: 590-597.
- 91 Duerschmied D. et al. Platelet serotonin promotes the recruitment of neutrophils to sites of acute inflammation in mice. Blood 2013; 121: 1008-1015.
- 92 Berger M. et al. The expanded biology of serotonin. Annu Rev Med 2009; 60: 355-366.
- 93 Mannaioni PF. et al. Storage and release of histamine in human platelets. Inflamm Res 1995; 44 (Suppl. 01) S16-17.
- 94 King SM. et al. Platelet dense-granule secretion plays a critical role in thrombosis and subsequent vascular remodeling in atherosclerotic mice. Circulation 2009; 120: 785-791.
- 95 Stefanini L. et al. CalDAG-GEFI is at the nexus of calcium-dependent platelet activation. Blood 2009; 112: 2506-2514.
- 96 Evangelista V. et al. Platelet/polymorphonuclear leukocyte interaction in dynamic conditions: evidence of adhesion cascade and cross talk between P-selectin and the beta 2 integrin CD11b/CD18. Blood 1996; 88: 4183-4194.
- 97 Frelinger AL 3rd. et al. The active metabolite of prasugrel inhibits ADP-stimulated thrombo-inflammatory markers of platelet activation: Influence of other blood cells, calcium, and aspirin. Thromb Haemost 2007; 98: 192-200.
- 98 Weissmann G. The role of lysosomes in inflammation and disease. Annu Rev Med 1967; 18: 97-112.
- 99 Sixma JJ. et al. Immuno-electron microscopical demonstration of lysosomes in human blood platelets and megakaryocytes using anti-cathepsin D. Blood 1985; 65: 1287-1291.
- 100 Radzun HJ. et al. Lysosomal acid phosphatase: activity and isoenzymes in separated normal human blood cells. Clin Chim Acta 1980; 102: 227-235.
- 101 Chesney CM. et al. Human platelet collagenase. J Clin Invest 1974; 53: 1647-1654.
- 102 Chappell D. et al. Heparinase selectively sheds heparan sulphate from the endothelial glycocalyx. Biol Chem 2008; 389: 79-82.
- 103 Dangelmaier CA, Holmsen H. Determination of acid hydrolases in human platelets. Analyt Biochem 1980; 104: 182-191.
- 104 Beaulieu LM. et al. Interleukin 1 Receptor 1 and Interleukin 1beta Regulate Megakaryocyte Maturation, Platelet Activation, and Transcript Profile During Inflammation in Mice and Humans. Arterioscler Thromb Vasc Biol. 2014 Epub ahead of print.
- 105 Maugeri N. et al. Circulating platelets as a source of the damage-associated molecular pattern HMGB1 in patients with systemic sclerosis. Autoimmunity 2012; 45: 584-587.
- 106 Rouhiainen A. et al. Occurrence of amphoterin (HMG1) as an endogenous protein of human platelets that is exported to the cell surface upon platelet activation. Thromb Haemost 2000; 84: 1087-1094.
- 107 Kraemer BF. et al. Novel anti-bacterial activities of beta-defensin 1 in human platelets: suppression of pathogen growth and signaling of neutrophil extracellular trap formation. PLoS Pathogens 2011; 7: e1002355.
- 108 Prancan A. et al. Platelet thromboxane production during endotoxin shock. Agents Actions 1981; 11: 648-650.
- 109 Edwards LJ, Constantinescu CS. Platelet activating factor/platelet activating factor receptor pathway as a potential therapeutic target in autoimmune diseases. Inflam Allergy Drug Targets 2009; 8: 182-190.
- 110 Aukrust P. et al. Enhanced levels of soluble and membrane-bound CD40 ligand in patients with unstable angina. Possible reflection of T lymphocyte and platelet involvement in the pathogenesis of acute coronary syndromes. Circulation 1999; 100: 614-620.
- 111 Leveille C. et al. CD40 ligand binds to alpha5beta1 integrin and triggers cell signaling. J Biol Chem 2007; 282: 5143-5151.
- 112 Schaff M. et al. Integrin alpha6beta1 is the main receptor for vascular laminins and plays a role in platelet adhesion, activation, and arterial thrombosis. Circulation 2013; 128: 541-552.
- 113 Bix G. et al. Endorepellin, the C-terminal angiostatic module of perlecan, enhances collagen-platelet responses via the alpha2beta1-integrin receptor. Blood 2007; 109: 3745-3748.
- 114 Yin H. et al. Role for platelet glycoprotein Ib-IX and effects of its inhibition in endotoxemia-induced thrombosis, thrombocytopenia, and mortality. Arterioscler Thromb Vasc Biol 2013; 33: 2529-2537.
- 115 Engelmann B, Massberg S. Thrombosis as an intravascular effector of innate immunity. Nat Rev Immunol 2013; 13: 34-45.
- 116 Verschoor A. et al. A platelet-mediated system for shuttling blood-borne bacteria to CD8alpha+ dendritic cells depends on glycoprotein GPIb and complement C3. Nature Immunol 2011; 12: 1194-1201.
- 117 Diacovo TG. et al. A functional integrin ligand on the surface of platelets: inter-cellular adhesion molecule-2. J Clin Invest 1994; 94: 1243-1251.
- 118 Weber KS. et al. Sialylation of ICAM-2 on platelets impairs adhesion of leukocytes via LFA-1 and DC-SIGN. Inflammation 2004; 28: 177-188.
- 119 Boulaftali Y. et al. Platelet ITAM signaling is critical for vascular integrity in inflammation. J Clin Invest 2013; 123: 908-916.
- 120 Schulz C. et al. Platelet GPVI binds to collagenous structures in the core region of human atheromatous plaque and is critical for atheroprogression in vivo. Basic Res Cardiol 2008; 103: 356-367.
- 121 Shiraki R. et al. Expression of Toll-like receptors on human platelets. Thromb Res 2004; 113: 379-385.
- 122 Beaulieu LM, Freedman JE. The role of inflammation in regulating platelet production and function: Toll-like receptors in platelets and megakaryocytes. Thromb Res 2010; 125: 205-209.
- 123 Koupenova M. et al. Platelet-TLR7 mediates host survival and platelet count during viral infection in the absence of platelet-dependent thrombosis. Blood. 2014 Epub ahead of print.
- 124 Koulis C. et al. Protective Role for Toll-Like Receptor-9 in the Development of Atherosclerosis in Apolipoprotein E-Deficient Mice. Arterioscler Thromb Vasc Biol. 2014 Epub ahead of print.
- 125 Lapchak PH. et al. Platelet-associated CD40/CD154 mediates remote tissue damage after mesenteric ischaemia/reperfusion injury. PLoS One 2012; 7: e32260.
- 126 Lievens D. et al. Platelet CD40L mediates thrombotic and inflammatory processes in atherosclerosis. Blood 2010; 116: 4317-4327.
- 127 Wolf D. et al. Binding of CD40L to Mac-1’s I-domain involves the EQLKKSKTL motif and mediates leukocyte recruitment and atherosclerosis--but does not affect immunity and thrombosis in mice. Circ Res 2011; 109: 1269-1279.
- 128 Lievens D. et al. The multi-functionality of CD40L and its receptor CD40 in atherosclerosis. Thromb Haemost 2009; 102: 206-214.
- 129 Gerdes N, Zirlik A. Co-stimulatory molecules in and beyond co-stimulation – tipping the balance in atherosclerosis?. Thromb Haemost 2011; 106: 804-813.
- 130 Haselmayer P. et al. TREM-1 ligand expression on platelets enhances neutrophil activation. Blood 2007; 110: 1029-1035.
- 131 Derive M. et al. Soluble TREM-like transcript-1 regulates leukocyte activation and controls microbial sepsis. J Immunol 2012; 188: 5585-5592.
- 132 Bergmeier W. et al. Tumor necrosis factor-alpha-converting enzyme (ADAM17) mediates GPIbalpha shedding from platelets in vitro and in vivo. Circ Res 2004; 95: 677-683.
- 133 Riaz AH. et al. Human platelets efficiently kill IgG-opsonized E. coli. FEMS Immunol Med Microbiol 2012; 65: 78-83.
- 134 Rogala B. et al. Platelet aggregation in IgE-mediated allergy with elevated soluble Fc epsilon RII/CD23 level. J Invest Allergol Clin Immunol 1995; 5: 161-165.
- 135 Qian K. et al. Functional expression of IgA receptor FcalphaRI on human platelets. J Leukoc Biol 2008; 84: 1492-1500.
- 136 Peerschke EI. et al. Platelet activation by C1q results in the induction of alpha IIb/beta 3 integrins (GPIIb-IIIa) and the expression of P-selectin and procoagulant activity. J Exp Med 1993; 178: 579-587.
- 137 Nguyen T. et al. Staphylococcus aureus protein A recognizes platelet gC1qR/p33: a novel mechanism for staphylococcal interactions with platelets. Infect Immun 2000; 68: 2061-2068.
- 138 Ando B. et al. The secretory release reaction initiated by complement proteins C5b-9 occurs without platelet aggregation through glycoprotein IIb-IIIa. Blood 1989; 73: 462-467.
- 139 Martel C. et al. Requirements for membrane attack complex formation and anaphylatoxins binding to collagen-activated platelets. PLoS One 2011; 6: e18812.
- 140 Hartwig H. et al. Platelet-derived PF4 reduces neutrophil apoptosis following arterial occlusion. Thromb Haemost 2014; 111: 562-564.
- 141 Gleissner CA. et al. Platelet chemokines in vascular disease. Arterioscler Thromb Vasc Biol 2008; 28: 1920-1927.
- 142 Verheul HM. et al. Platelets take up the monoclonal antibody bevacizumab. Clin Cancer Res 2007; 13: 5341-5347.
- 143 de Jong JS, Dekker LR. Platelets and cardiac arrhythmia. Frontiers Physiol 2010; 1: 166.
- 144 McNicol A, Israels SJ. Platelet dense granules: structure, function and implications for haemostasis. Thromb Res 1999; 95: 1-18.
- 145 Kenis G, Maes M. Effects of antidepressants on the production of cytokines. Int J Neuropsychopharmacol 2002; 5: 401-412.
- 146 Durk T. et al. 5-Hydroxytryptamine modulates cytokine and chemokine production in LPS-primed human monocytes via stimulation of different 5-HTR subtypes. Int Immunol 2005; 17: 599-606.
- 147 Walther DJ. et al. Synthesis of serotonin by a second tryptophan hydroxylase isoform. Science 2003; 299: 76.
- 148 Iken K. et al. Serotonin upregulates mitogen-stimulated B lymphocyte proliferation through 5-HT1A receptors. Cell Immunol 1995; 163: 1-9.
- 149 Ito T. et al. Serotonin increases interleukin-6 synthesis in human vascular smooth muscle cells. Circulation 2000; 102: 2522-2527.
- 150 Yu B. et al. Serotonin 5-hydroxytryptamine(2A) receptor activation suppresses tumor necrosis factor-alpha-induced inflammation with extraordinary potency. J Pharmacol Exp Ther 2008; 327: 316-323.
- 151 Muller T. et al. 5-hydroxytryptamine modulates migration, cytokine and chemokine release and T-cell priming capacity of dendritic cells in vitro and in vivo. PLoS One 2009; 4: e6453.
- 152 Walther A. et al. Selective serotonin-receptor antagonism and microcirculatory alterations during experimental endotoxemia. J Surg Res 2007; 143: 216-223.
- 153 Schuff-Werner P, Splettstoesser W. Antioxidative properties of serotonin and the bactericidal function of polymorphonuclear phagocytes. Adv Exp Med Biol 1999; 467: 321-325.
- 154 Ciz M. et al. Serotonin modulates the oxidative burst of human phagocytes via various mechanisms. Platelets 2007; 18: 583-590.
- 155 Pracharova L. et al. Serotonin and its 5-HT(2) receptor agonist DOI hydro-chloride inhibit the oxidative burst in total leukocytes but not in isolated neutrophils. Life Sci 2010; 86: 518-523.
- 156 Bondesson L. et al. Inhibiting effects of serotonin and serotonin antagonists on the migration of mononuclear leucocytes. Immunopharmacol Immunotoxicol 1993; 15: 243-250.
- 157 Northover BJ. The effect of histamine and 5-hydroxytryptamine on phagocytosis of staphylococci in vitro by polymorphs and macrophages. J Pathol Bacteriol 1961; 82: 355-361.
- 158 Nordlind K. et al. Inhibiting effects of serotonin antagonists on the proliferation of mercuric chloride stimulated human peripheral blood T lymphocytes. Int Arch Allergy Immunol 1992; 97: 105-108.
- 159 Sternberg EM. et al. Effect of serotonin on murine macrophages: suppression of Ia expression by serotonin and its reversal by 5-HT2 serotonergic receptor antagonists. J Immunol 1986; 137: 276-282.
- 160 Hellstrand K. et al. Role of serotonin in the regulation of interferon-gamma production by human natural killer cells. J Interferon Res 1993; 13: 33-38.
- 161 Young MR, Matthews JP. Serotonin regulation of T-cell subpopulations and of macrophage accessory function. Immunology 1995; 84: 148-152.
- 162 Kut JL. et al. Regulation of murine T-lymphocyte function by spleen cell-derived and exogenous serotonin. Immunopharmacol Immunotoxicol 1992; 14: 783-796.
- 163 Arzt E. et al. Serotonin inhibition of tumor necrosis factor-alpha synthesis by human monocytes. Life Sci 1991; 48: 2557-2562.
- 164 Cloez-Tayarani I. et al. Differential effect of serotonin on cytokine production in lipopolysaccharide-stimulated human peripheral blood mononuclear cells: involvement of 5-hydroxytryptamine2A receptors. Int Immunol 2003; 15: 233-240.
- 165 Kubera M. et al. Effects of serotonin and serotonergic agonists and antagonists on the production of tumor necrosis factor alpha and interleukin-6. Psychiatry Res 2005; 134: 251-258.
- 166 Tohidnezhad M. et al. Platelets display potent antimicrobial activity and release human beta-defensin 2. Platelets 2012; 23: 217-223.
- 167 Tohidnezhad M. et al. Thrombocytes are effectors of the innate immune system releasing human beta defensin-3. Injury 2011; 42: 682-686.
- 168 Kasirer-Friede A. et al. Platelet integrins and immunoreceptors. Immunol Rev 2007; 218: 247-264.
- 169 Peerschke EI. et al. Platelet mediated complement activation. Adv Exp Med Biol 2008; 632: 81-91.
- 170 Ginsberg MH, Henson PM. Enhancement of platelet response to immune complexes and IgG aggregates by lipid A-rich bacterial lipopolysaccharides. J Exp Med 1978; 147: 207-217.
- 171 Lister KJ. et al. Immune complexes mediate rapid alterations in microvascular permeability: roles for neutrophils, complement, and platelets. Microcirculation 2007; 14: 709-722.
- 172 Suzuki-Inoue K. Essential in vivo roles of the platelet activation receptor CLEC-2 in tumour metastasis, lymphangiogenesis and thrombus formation. J Biochem 2011; 150: 127-132.
- 173 Elzey BD. et al. Platelet CD40L at the interface of adaptive immunity. Thromb Res 2011; 127: 180-183.
- 174 Ferroni P. et al. Contribution of platelet-derived CD40 ligand to inflammation, thrombosis and neoangiogenesis. Curr Med Chem 2007; 14: 2170-2180.
- 175 Lutgens E. et al. Deficient CD40-TRAF6 signaling in leukocytes prevents atherosclerosis by skewing the immune response toward an antiinflammatory profile. J Exp Med 2010; 207: 391-404.
- 176 Zirlik A. et al. TRAF-1, –2, –3, –5, and –6 are induced in atherosclerotic plaques and differentially mediate proinflammatory functions of CD40L in endothelial cells. Arterioscler Thromb Vasc Biol 2007; 27: 1101-1107.
- 177 Lutgens E. et al. CD40L-CD40 fuel ignites obesity. Thromb Haemost 2010; 103: 694-695.
- 178 Henn V. et al. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature 1998; 391: 591-594.
- 179 Andonegui G. et al. Platelets express functional Toll-like receptor-4. Blood 2005; 106: 2417-2423.
- 180 Rex S. et al. Immune versus thrombotic stimulation of platelets differentially regulates signalling pathways, intracellular protein-protein interactions, and alpha-granule release. Thromb Haemost 2009; 102: 97-110.
- 181 Blair P. et al. Stimulation of Toll-like receptor 2 in human platelets induces a thromboinflammatory response through activation of phosphoinositide 3-kinase. Circ Res 2009; 104: 346-354.
- 182 Thon JN. et al. T granules in human platelets function in TLR9 organisation and signaling. J Cell Biol 2012; 198: 561-574.
- 183 Cognasse F. et al. Evidence of Toll-like receptor molecules on human platelets. Immunol Cell Biol 2005; 83: 196-198.
- 184 Aslam R. et al. Platelet Toll-like receptor expression modulates lipopolysaccharide-induced thrombocytopenia and tumor necrosis factor-alpha production in vivo. Blood 2006; 107: 637-641.
- 185 Berthet J. et al. Human platelets can discriminate between various bacterial LPS isoforms via TLR4 signaling and differential cytokine secretion. Clin Immunol 2012; 145: 189-200.
- 186 Zhang G. et al. Lipopolysaccharide stimulates platelet secretion and potentiates platelet aggregation via TLR4/MyD88 and the cGMP-dependent protein kinase pathway. J Immunol 2009; 182: 7997-8004.
- 187 Falker K. et al. The toll-like receptor 2/1 (TLR2/1) complex initiates human platelet activation via the src/Syk/LAT/PLCgamma2 signalling cascade. Cell Signal 2014; 26: 279-286.
- 188 Rivadeneyra L. et al. Regulation of platelet responses triggered by Toll-like receptor 2 and 4 ligands is another non-genomic role of nuclear factor-kappaB. Thromb Res 2014; 133: 235-243.
- 189 Clark SR. et al. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med 2007; 13: 463-469.
- 190 Panigrahi S. et al. Engagement of platelet toll-like receptor 9 by novel endogenous ligands promotes platelet hyperreactivity and thrombosis. Circ Res 2013; 112: 103-112.
- 191 Li Y. et al. ADAM17 deficiency by mature neutrophils has differential effects on L-selectin shedding. Blood 2006; 108: 2275-2279.
- 192 Black RA. et al. A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells. Nature 1997; 385: 729-733.
- 193 Canault M. et al. Microparticles of human atherosclerotic plaques enhance the shedding of the tumor necrosis factor-alpha converting enzyme/ADAM17 substrates, tumor necrosis factor and tumor necrosis factor receptor-1. Am J Pathol 2007; 171: 1713-1723.
- 194 Canault M. et al. The TNF alpha converting enzyme (TACE/ADAM17) is expressed in the atherosclerotic lesions of apolipoprotein E-deficient mice: possible contribution to elevated plasma levels of soluble TNF alpha receptors. Atherosclerosis 2006; 187: 82-91.
- 195 Duerschmied D. et al. Serotonin stimulates platelet receptor shedding by tumor necrosis factor-alpha-converting enzyme (ADAM17). J Thromb Haemost 2009; 7: 1163-1171.
- 196 Peschon JJ. et al. An essential role for ectodomain shedding in mammalian development. Science 1998; 282: 1281-1284.
- 197 Brill A. et al. Oxidative stress activates ADAM17/TACE and induces its target receptor shedding in platelets in a p38-dependent fashion. Cardiovasc Res 2009; 84: 137-144.
- 198 Assinger A. et al. Efficient phagocytosis of periodontopathogens by neutrophils requires plasma factors, platelets and TLR2. J Thromb Haemost 2011; 9: 799-809.
- 199 Pamuk GE. et al. Increased circulating platelet-neutrophil, platelet-monocyte complexes, and platelet activation in patients with ulcerative colitis: a comparative study. Am J Hematol 2006; 81: 753-759.
- 200 Braun OO. et al. Greater reduction of platelet activation markers and platelet-monocyte aggregates by prasugrel compared to clopidogrel in stable coronary artery disease. Thromb Haemost 2008; 100: 626-633.
- 201 da Costa Martins P. et al. Platelet-monocyte complexes support monocyte adhesion to endothelium by enhancing secondary tethering and cluster formation. Arterioscler Thromb Vasc Biol 2004; 24: 193-199.
- 202 Sanderson HM. et al. Role of GPIIb-IIIa in platelet-monocyte and platelet-neutrophil conjugate formation in whole blood. Platelets 1998; 9: 245-250.
- 203 Herr N. et al. Acute fluoxetine treatment induces slow rolling of leukocytes on endothelium in mice. PLoS One 2014; 9: e88316.
- 204 Weber C, Springer TA. Neutrophil accumulation on activated, surface-adherent platelets in flow is mediated by interaction of Mac-1 with fibrinogen bound to alphaIIbbeta3 and stimulated by platelet-activating factor. J Clin Invest 1997; 100: 2085-2093.
- 205 Simon DI. et al. Platelet glycoprotein ibalpha is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18). J Exp Med 2000; 192: 193-204.
- 206 Kastrup CJ. et al. Spatial localisation of bacteria controls coagulation of human blood by ’quorum acting’. Nature chemical biology 2008; 4: 742-750.
- 207 Youssefian T. et al. Host defense role of platelets: engulfment of HIV and Staphylococcus aureus occurs in a specific subcellular compartment and is enhanced by platelet activation. Blood 2002; 99: 4021-4029.
- 208 Zarbock A. et al. Leukocyte ligands for endothelial selectins: specialized glycoconjugates that mediate rolling and signaling under flow. Blood 2011; 118: 6743-6751.
- 209 Sarma J. et al. Increased platelet binding to circulating monocytes in acute coronary syndromes. Circulation 2002; 105: 2166-2171.
- 210 Clark RA, Klebanoff SJ. Neutrophil-platelet interaction mediated by myeloperoxidase and hydrogen peroxide. J Immunol 1980; 124: 399-405.
- 211 Nieswandt B. et al. Integrins in platelet activation. J Thromb Haemost 2009; 7 (Suppl. 01) 206-209.
- 212 van Gils JM. et al. Molecular and functional interactions among monocytes, platelets, and endothelial cells and their relevance for cardiovascular diseases. J Leukoc Biol 2009; 85: 195-204.
- 213 Michelson AD. Methods for the measurement of platelet function. Am J Cardiol 2009; 103 (03) Suppl 20A-26A.
- 214 Michelson AD. Platelet function testing in cardiovascular diseases. Circulation 2004; 110: e489-493.
- 215 Langer HF. et al. Platelets contribute to the pathogenesis of experimental auto-immune encephalomyelitis. Circ Res 2012; 110: 1202-1210.
- 216 Wilson M. et al. Effects in humans of intravenously administered endotoxin on soluble cell-adhesion molecule and inflammatory markers: a model of human diseases. Clin Exp Pharmacol Physiol 2001; 28: 376-380.
- 217 Kalsch T. et al. Endotoxin-induced effects on platelets and monocytes in an in vivo model of inflammation. Basic Res Cardiol 2007; 102: 460-466.
- 218 Passacquale G. et al. Monocyte-platelet interaction induces a pro-inflammatory phenotype in circulating monocytes. PLoS One 2011; 6: e25595.
- 219 Kuckleburg CJ. et al. Endothelial cell-borne platelet bridges selectively recruit monocytes in human and mouse models of vascular inflammation. Cardiovasc Res 2011; 91: 134-141.
- 220 Goncalves R. et al. Platelet activation attracts a subpopulation of effector monocytes to sites of Leishmania major infection. J Exp Med 2011; 208: 1253-1265.
- 221 Lam FW. et al. Platelets enhance neutrophil transendothelial migration via P-selectin glycoprotein ligand-1. Am J Physiol Heart Circ Physiol 2011; 300: H468-475.
- 222 Brinkmann V. et al. Neutrophil extracellular traps kill bacteria. Science 2004; 303: 1532-1535.
- 223 Jenne CN. et al. Neutrophils recruited to sites of infection protect from virus challenge by releasing neutrophil extracellular traps. Cell Host Microbe 2013; 13: 169-180.
- 224 McDonald B. et al. Intravascular neutrophil extracellular traps capture bacteria from the bloodstream during sepsis. Cell Host Microbe 2012; 12: 324-333.
- 225 Megens RT. et al. Presence of luminal neutrophil extracellular traps in atherosclerosis. Thromb Haemost 2012; 107: 597-598.
- 226 Borissoff JI. et al. Elevated levels of circulating DNA and chromatin are independently associated with severe coronary atherosclerosis and a prothrombotic state. Arterioscler Thromb Vasc Biol 2013; 33: 2032-2040.
- 227 Fuchs TA. et al. Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci USA 2010; 107: 15880-15885.
- 228 Fuchs TA. et al. Circulating DNA and myeloperoxidase indicate disease activity in patients with thrombotic microangiopathies. Blood 2012; 120: 1157-1164.
- 229 Schwarz M. et al. Conformation-specific blockade of the integrin GPIIb/IIIa: a novel antiplatelet strategy that selectively targets activated platelets. Circ Res 2006; 99: 25-33.
- 230 Wang X. et al. Novel single-chain antibody-targeted microbubbles for molecular ultrasound imaging of thrombosis: validation of a unique noninvasive method for rapid and sensitive detection of thrombi and monitoring of success or failure of thrombolysis in mice. Circulation 2012; 125: 3117-3126.
- 231 von Zur Muhlen C. et al. A contrast agent recognizing activated platelets reveals murine cerebral malaria pathology undetectable by conventional MRI. J Clin Invest 2008; 118: 1198-1207.
- 232 McAteer MA. et al. In vivo magnetic resonance imaging of acute brain inflammation using microparticles of iron oxide. Nat Med 2007; 13: 1253-1258.
- 233 Duerschmied D. et al. Molecular magnetic resonance imaging allows the detection of activated platelets in a new mouse model of coronary artery thrombosis. Invest Radiol 2011; 46: 618-623.
- 234 Wang X. et al. Towards Effective and Safe Thrombolysis and Thromboprophylaxis: Preclinical Testing of a Novel Antibody-Targeted Recombinant Plasminogen Activator Directed Against Activated Platelets. Circ Res. 2014 Epub ahead of print.
- 235 von Zur Muhlen C. et al. Magnetic Resonance Imaging Contrast Agent Targeted Toward Activated Platelets Allows In Vivo Detection of Thrombosis and Monitoring of Thrombolysis. Circulation 2008; 118: 258-267.
- 236 Steiner S. et al. Effect of glycoprotein IIb/IIIa antagonist abciximab on monocyte-platelet aggregates and tissue factor expression. Arterioscler Thromb Vasc Biol 2003; 23: 1697-1702.