Subscribe to RSS
DOI: 10.1160/TH13-02-0096
Platelets and neurovascular inflammation
Publication History
Received: 04 February 2013
Accepted after major revision: 25 March 2013
Publication Date:
01 December 2017 (online)
Summary
Platelets participate in haemostasis and in thrombus formation in health and disease. Moreover, they contribute to inflammation and cooperate with immune cells in a magnitude of inflammatory/immune responses. Although the inflammatory response has been recognised to be critical in neuronal diseases such as Alzheimer´s disease or multiple sclerosis and its mouse counterpart, experimental autoimmune encephalomyelitis, the participation of platelets in these diseases is poorly investigated so far. Emerging studies, however, point to an interesting crosstalk between platelets and neuroinflammation. For instance, when the integrity of the blood brain barrier is compromised, platelets may be relevant for endothelial inflammation, as well as recruitment and activation of inflammatory cells, thereby potentially contributing to central nervous tissue pathogenesis. This review summarises recent insights in the role of platelets for neurovascular inflammation and addresses potential underlying mechanisms, by which platelets may affect the pathophysiology of neurovascular diseases.
-
References
- 1 Langer HF, Chavakis T. Leukocyte-endothelial interactions in inflammation. J Cell Mol Med 2009; 13: 1211-1220.
- 2 von Hundelshausen P, Weber C. Platelets as immune cells: bridging inflammation and cardiovascular disease. Circ Res 2007; 100: 27-40.
- 3 von Hundelshausen P, Koenen RR, Weber C. Platelet-mediated enhancement of leukocyte adhesion. Microcirculation 2009; 16: 84-96.
- 4 Gawaz M, Langer H, May AE. Platelets in inflammation and atherogenesis. J Clin Invest 2005; 115: 3378-3384.
- 5 Wagner DD, Frenette PS. The vessel wall and its interactions. Blood 2008; 111: 5271-5281.
- 6 Ehlers R, Ustinov V, Chen Z. et al. Targeting platelet-leukocyte interactions: identification of the integrin Mac-1 binding site for the platelet counter receptor glycoprotein Ibalpha. J Exp Med 2003; 198: 1077-1088.
- 7 Simon DI, 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.
- 8 Santoso S, Sachs UJ, 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: 679-691.
- 9 Chavakis T, Santoso S, Clemetson KJ. et al. High molecular weight kininogen regulates platelet-leukocyte interactions by bridging Mac-1 and glycoprotein Ib. J Biol Chem 2003; 278: 45375-45381.
- 10 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.
- 11 Simon DI. Inflammation and vascular injury: basic discovery to drug development. Circ J 2012; 76: 1811-1818.
- 12 Langer HF, Choi EY, Zhou H. et al. Platelets Contribute to the Pathogenesis of Experimental Autoimmune Encephalomyelitis. Circ Res 2012; 110: 1202-1210.
- 13 Wang Y, Sakuma M, Chen Z. et al. Leukocyte engagement of platelet glycoprotein Ibalpha via the integrin Mac-1 is critical for the biological response to vascular injury. Circulation 2005; 112: 2993-3000.
- 14 Boilard E, Nigrovic PA, Larabee K. et al. Platelets amplify inflammation in arthritis via collagen-dependent microparticle production. Science 2010; 327: 580-583.
- 15 Clark SR, Ma AC, Tavener SA. et al. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med 2007; 13: 463-469.
- 16 Mause SF, Weber C. Microparticles: protagonists of a novel communication network for intercellular information exchange. Circ Res 2010; 107: 1047-1057.
- 17 Mause SF, von Hundelshausen P, Zernecke A. et al. Platelet microparticles: a transcellular delivery system for RANTES promoting monocyte recruitment on endothelium. Arterioscler Thromb Vasc Biol 2005; 25: 1512-1518.
- 18 Vasina E, Heemskerk JW, Weber C. et al. Platelets and platelet-derived microparticles in vascular inflammatory disease. Inflamm Allergy Drug Targets 2010; 9: 346-354.
- 19 Vasina EM, Cauwenberghs S, Feijge MA. et al. Microparticles from apoptotic platelets promote resident macrophage differentiation. Cell Death Dis 2011; 2: e211
- 20 Alexandru N, Popov D, Dragan E. et al. Circulating endothelial progenitor cell and platelet microparticle impact on platelet activation in hypertension associated with hypercholesterolemia. PLoS One 2013; 8: e52058
- 21 Amabile N, Rautou PE, Tedgui A, Boulanger CM. Microparticles: key protagonists in cardiovascular disorders. Semin Thromb Hemost 2010; 36: 907-916.
- 22 Dasgupta SK, Le A, Chavakis T. et al. Developmental endothelial locus-1 (Del-1) mediates clearance of platelet microparticles by the endothelium. Circulation 2012; 125: 1664-1672.
- 23 Zhou H, Lapointe BM, Clark SR. et al. A requirement for microglial TLR4 in leukocyte recruitment into brain in response to lipopolysaccharide. J Immunol 2006; 177: 8103-8110.
- 24 Zhou H, Andonegui G, Wong CH. et al. Role of endothelial TLR4 for neutrophil recruitment into central nervous system microvessels in systemic inflammation. J Immunol 2009; 183: 5244-5250.
- 25 Adams RA, Bauer J, Flick MJ. et al. The fibrin-derived gamma377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease. J Exp Med 2007; 204: 571-582.
- 26 Davalos D, Ryu JK, Merlini M. et al. Fibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation. Nat Commun 2012; 3: 1227
- 27 Carvalho-Tavares J, Hickey MJ, Hutchison J. et al. A role for platelets and endothelial selectins in tumor necrosis factor-alpha-induced leukocyte recruitment in the brain microvasculature. Circ Res 2000; 87: 1141-1148.
- 28 von zur Muhlen C, Sibson NR, Peter K. et al. A contrast agent recognizing activated platelets reveals murine cerebral malaria pathology undetectable by conventional MRI. J Clin Invest 2008; 118: 1198-1207.
- 29 Barbier M, Faille D, Loriod B. et al. Platelets alter gene expression profile in human brain endothelial cells in an in vitro model of cerebral malaria. PLoS One 2011; 6: e19651
- 30 Lindemann S, Tolley ND, Dixon DA. et al. Activated platelets mediate inflammatory signaling by regulated interleukin 1beta synthesis. J Cell Biol 2001; 154: 485-490.
- 31 Weyrich AS, Zimmerman GA. Platelets: signaling cells in the immune continuum. Trends Immunol 2004; 25: 489-495.
- 32 Patzelt J, Langer HF. Platelets in angiogenesis. Curr Vasc Pharmacol 2012; 10: 570-577.
- 33 Thornton P, McColl BW, Greenhalgh A. et al. Platelet interleukin-1alpha drives cerebrovascular inflammation. Blood 2010; 115: 3632-3639.
- 34 Nieswandt B, Kleinschnitz C, Stoll G. Ischaemic stroke: a thrombo-inflammatory disease?. J Physiol 2011; 589: 4115-4123.
- 35 Stoll G, Kleinschnitz C, Nieswandt B. Molecular mechanisms of thrombus formation in ischemic stroke: novel insights and targets for treatment. Blood 2008; 112: 3555-3562.
- 36 Kleinschnitz C, Pozgajova M, Pham M. et al. Targeting platelets in acute experimental stroke: impact of glycoprotein Ib, VI, and IIb/IIIa blockade on infarct size, functional outcome, and intracranial bleeding. Circulation 2007; 115: 2323-2330.
- 37 Langhauser F, Gob E, Kraft P. et al. Kininogen deficiency protects from ischemic neurodegeneration in mice by reducing thrombosis, blood-brain barrier damage, and inflammation. Blood 2012; 120: 4082-4092.
- 38 Kleinschnitz C, Schwab N, Kraft P. et al. Early detrimental T-cell effects in experimental cerebral ischemia are neither related to adaptive immunity nor thrombus formation. Blood 2010; 115: 3835-3842.
- 39 Kleinschnitz C, Kraft P, Dreykluft A. et al. Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature. Blood 2013; 121: 679-691.
- 40 De Meyer SF, Stoll G, Wagner DD, Kleinschnitz C. von Willebrand factor: an emerging target in stroke therapy. Stroke 2012; 43: 599-606.
- 41 Kleinschnitz C, Pozgajova M, Pham M. et al. Targeting platelets in acute experimental stroke: impact of glycoprotein Ib, VI, and IIb/IIIa blockade on infarct size, functional outcome, and intracranial bleeding. Circulation 2007; 115: 2323-2330.
- 42 Elvers M, Stegner D, Hagedorn I. et al. Impaired alpha(IIb)beta(3) integrin activation and shear-dependent thrombus formation in mice lacking phospholipase D1. Sci Signal 2010; 3: 1-10.
- 43 Doeuvre L, Plawinski L, Toti F. et al. Cell-derived microparticles: a new challenge in neuroscience. J Neurochem 2009; 110: 457-468.
- 44 Simak J, Gelderman MP, Yu H. et al. Circulating endothelial microparticles in acute ischemic stroke: a link to severity, lesion volume and outcome. J Thromb Haemost 2006; 4: 1296-1302.
- 45 Lukasik M, Rozalski M, Luzak B. et al. Platelet activation and reactivity in the convalescent phase of ischaemic stroke. Thromb Haemost 2010; 103: 644-650.
- 46 Querfurth HW, LaFerla FM. Alzheimer's disease. N Engl J Med 2010; 362: 329-344.
- 47 Sardi F, Fassina L, Venturini L. et al. Alzheimer's disease, autoimmunity and inflammation. The good, the bad and the ugly. Autoimmun Rev 2011; 11: 149-153.
- 48 Claeysen S, Cochet M, Donneger R. et al. Alzheimer culprits: cellular crossroads and interplay. Cell Signal 2012; 24: 1831-1840.
- 49 Eisenberg D, Jucker M. The amyloid state of proteins in human diseases. Cell 2012; 148: 1188-1203.
- 50 Jucker M. The benefits and limitations of animal models for translational research in neurodegenerative diseases. Nat Med 2010; 16: 1210-1214.
- 51 Devanand DP, Mintzer J, Schultz SK. et al. Relapse risk after discontinuation of risperidone in Alzheimer's disease. N Engl J Med 2012; 367: 1497-1507.
- 52 Nussbaum JM, Seward ME, Bloom GS. Alzheimer disease: A tale of two prions. Prion 2012; 7: 14-19.
- 53 de Silva HA, Aronson JK, Grahame-Smith DG. et al. Abnormal function of potassium channels in platelets of patients with Alzheimer's disease. Lancet 1998; 352: 1590-1593.
- 54 Sevush S, Jy W, Horstman LL. et al. Platelet activation in Alzheimer disease. Arch Neurol 1998; 55: 530-536.
- 55 Bush AI, Tanzi RE. Alzheimer disease-related abnormalities of amyloid beta precursor protein isoforms in the platelet: the brain's delegate in the periphery?. Arch Neurol 1998; 55: 1179-1180.
- 56 Catricala’ S, Torti M, Ricevuti G. Alzheimer disease and platelets: how's that relevant. Immun Ageing 2012; 9: 20
- 57 Skovronsky DM, Lee VM, Pratico D. Amyloid precursor protein and amyloid beta peptide in human platelets. Role of cyclooxygenase and protein kinase C. J Biol Chem 2001; 276: 17036-17043.
- 58 Zainaghi IA, Talib LL, Diniz BS. et al. Reduced platelet amyloid precursor protein ratio (APP ratio) predicts conversion from mild cognitive impairment to Alzheimer's disease. J Neural Transm 2012; 119: 815-819.
- 59 Vignini A, Sartini D, Morganti S. et al. Platelet amyloid precursor protein isoform expression in Alzheimer's disease: evidence for peripheral marker. Int J Immunopathol Pharmacol 2011; 24: 529-534.
- 60 Laske C, Leyhe T, Stransky E. et al. Association of platelet-derived soluble glycoprotein VI in plasma with Alzheimer's disease. J Psychiatr Res 2008; 42: 746-751.
- 61 Stellos K, Panagiota V, Kogel A. et al. Predictive value of platelet activation for the rate of cognitive decline in Alzheimer's disease patients. J Cereb Blood Flow Metab 2010; 30: 1817-1820.
- 62 Neumann K, Farias G, Slachevsky A. et al. Human platelets tau: a potential peripheral marker for Alzheimer's disease. J Alzheimers Dis 2011; 25: 103-109.
- 63 Ursini F, Davies KJ, Maiorino M. et al. Atherosclerosis: another protein misfolding disease?. Trends Mol Med 2002; 8: 370-374.
- 64 Herczenik E, Bouma B, Korporaal SJ. et al. Activation of human platelets by misfolded proteins. Arterioscler Thromb Vasc Biol 2007; 27: 1657-1665.
- 65 Ray DM, Spinelli SL, O'Brien JJ. et al. Platelets as a novel target for PPARgamma ligands : implications for inflammation, diabetes, and cardiovascular disease. BioDrugs 2006; 20: 231-241.
- 66 Bishop-Bailey D. The platelet as a model system for the acute actions of nuclear receptors. Steroids 2010; 75: 570-575.
- 67 Sodhi RK, Singh N, Jaggi AS. Neuroprotective mechanisms of peroxisome proliferator-activated receptor agonists in Alzheimer's disease. Naunyn Schmiedebergs Arch Pharmacol 2011; 384: 115-124.
- 68 Jaturapatporn D, Isaac MG, McCleery J. et al. Aspirin, steroidal and non-steroidal anti-inflammatory drugs for the treatment of Alzheimer's disease. Cochrane Database Syst Rev 2012; 2: CD006378
- 69 Thoonsen H, Richard E, Bentham P. et al. Aspirin in Alzheimer's disease: increased risk of intracerebral hemorrhage: cause for concern?. Stroke 2010; 41: 2690-2692.
- 70 Steinman L. Elaborate interactions between the immune and nervous systems. Nat Immunol 2004; 5: 575-581.
- 71 Steinman L, Martin R, Bernard C. et al. Multiple sclerosis: deeper understanding of its pathogenesis reveals new targets for therapy. Annu Rev Neurosci 2002; 25: 491-505.
- 72 Steinman L. Blocking adhesion molecules as therapy for multiple sclerosis: natalizumab. Nat Rev Drug Discov 2005; 4: 510-518.
- 73 Yednock TA, Cannon C, Fritz LC. et al. Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin. Nature 1992; 356: 63-66.
- 74 Graesser D, Solowiej A, Bruckner M. et al. Altered vascular permeability and early onset of experimental autoimmune encephalomyelitis in PECAM-1-deficient mice. J Clin Invest 2002; 109: 383-392.
- 75 Vajkoczy P, Laschinger M, Engelhardt B. Alpha4-integrin-VCAM-1 binding mediates G protein-independent capture of encephalitogenic T cell blasts to CNS white matter microvessels. J Clin Invest 2001; 108: 557-565.
- 76 Steinman L. The discovery of natalizumab, a potent therapeutic for multiple sclerosis. J Cell Biol 2012; 199: 413-416.
- 77 Lock C, Hermans G, Pedotti R. et al. Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat Med 2002; 8: 500-508.
- 78 Doring A, Wild M, Vestweber D. et al. E- and P-selectin are not required for the development of experimental autoimmune encephalomyelitis in C57BL/6 and SJL mice. J Immunol 2007; 179: 8470-8479.
- 79 Bullard DC, Hu X, Schoeb TR, Axtell RC, Raman C, Barnum SR. Critical requirement of CD11b (Mac-1) on T cells and accessory cells for development of experimental autoimmune encephalomyelitis. J Immunol 2005; 175: 6327-6333.
- 80 Sheremata WA, Jy W, Horstman LL, Ahn YS, Alexander JS, Minagar A. Evidence of platelet activation in multiple sclerosis. J Neuroinflammation 2008; 5: 27
- 81 Han MH, Hwang SI, Roy DB. et al. Proteomic analysis of active multiple sclerosis lesions reveals therapeutic targets. Nature 2008; 451: 1076-1081.
- 82 Horstman LL, Jy W, Ahn YS. et al. Role of platelets in neuroinflammation: a wide-angle perspective. J Neuroinflammation 2010; 7: 10