The prowess of platelets in immunity and inflammation

Rory R. Koenen

doi:10.1160/TH16-04-0300

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2016; 116(04): 605-612
DOI: 10.1160/TH16-04-0300

Theme Issue Article

Schattauer GmbH

The prowess of platelets in immunity and inflammation

Rory R. Koenen

¹Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands

²Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University Munich, Munich, Germany

› Author Affiliations

Abstract

Summary

Platelets not only serve as essential haemostatic cells, they also have important roles in immune defence and inflammation. Despite not having a nucleus, platelets contain physiologically relevant amounts of RNA, which can be spliced and translated into functional proteins. In addition, platelets have the ability to bind to numerous other cells, such as leukocytes and vascular cells. During those interactions, platelets can modulate cellular responses, resulting in e. g. inflammatory activation or apoptosis. Recent studies have demonstrated that platelets can influence the outcomes of bacterial and viral infection, as well as the extent of tissue injury after ischaemia. Platelets also carry considerable amounts of cytokines and growth factors in their secretory granules, preformed for rapid secretion. Those properties in combination with the sheer amount of platelets circulating in the blood stream make them an important force in the immune response during health and disease. In this overview, recent findings concerning those interesting properties of platelets beyond haemostasis are discussed.

Keywords

Platelet immunology - inflammation - chemokines - adhesion molecules

Full Text

References

References
1 Semple JW. et al. Platelets and the immune continuum. Nat Rev Immunol 2011; 11: 264-274.
2 Rondina MT. et al. Platelets as cellular effectors of inflammation in vascular diseases. Circ Res 2013; 112: 1506-1519.
3 Projahn D, Koenen RR.. Platelets: key players in vascular inflammation. J Leuk Biol 2012; 92: 1167-1175.
4 Jenne CN, Kubes P.. Platelets in inflammation and infection. Platelets 2015; 26: 286-292.
5 Duerschmied D. et al. Immune functions of platelets. Thromb Haemost 2014; 112: 678-691.
6 Thomas MR, Storey RF.. The role of platelets in inflammation. Thromb Haemost 2015; 114: 449-458.
7 Ruggeri ZM, Mendolicchio GL.. Adhesion mechanisms in platelet function. Circ Res 2007; 100: 1673-1685.
8 Vajen T. et al. Microvesicles from platelets: novel drivers of vascular inflammation. Thromb Haemost 2015; 114: 228-236.
9 Jurk K, Kehrel BE.. Platelets: physiology and biochemistry. Semin Thromb Hemost 2005; 31: 381-392.
10 Heemskerk JWM. et al. Platelet-based coagulation: different populations, different functions. J Thromb Haemost 2013; 11: 2-16.
11 Bye AP. et al. Platelet signaling: a complex interplay between inhibitory and activatory networks. J Thromb Haemost 2016; 14: 918-930.
12 Kehrel B. 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: 491-499.
13 Golebiewska EM, Poole AW.. Platelet secretion: From haemostasis to wound healing and beyond. Blood Rev 2015; 29: 153-162.
14 Deppermann C. et al. Gray platelet syndrome and defective thrombo-inflammation in Nbea12-deficient mice. J Clin Invest 2013; 123: 3331-3342.
15 Konopatskaya O. et al. PKCalpha regulates platelet granule secretion and thrombus formation in mice. J Clin Invest 2009; 119: 399-407.
16 Junt T, Schulze H, Chen Z. et al. Dynamic visualisation of thrombopoiesis within bone marrow. Science 2007; 317: 1767-1770.
17 Machlus KR, Italiano JE.. The incredible journey: From megakaryocyte development to platelet formation. J Cell Biol 2013; 201: 785-796.
18 Denis MM. et al. Escaping the nuclear confines: signal-dependent pre-mRNA splicing in anucleate platelets. Cell 2005; 122: 379-391.
19 Schwertz H. et al. Anucleate platelets generate progeny. Blood 2010; 115: 3801-3809.
20 Mason KD, Carpinelli MR, Fletcher JI. et al. Programmed anuclear cell death delimits platelet life span. Cell 2007; 128: 1173-1186.
21 Ouseph MM. et al. Autophagy is induced upon platelet activation and is essential for hemostasis and thrombosis. Blood 2015; 126: 1224-1233.
22 Kieffer N. et al. Biosynthesis of major platelet proteins in human blood platelets. Eur J Biochem 1987; 164: 189-195.
23 Lindemann S. et al. Activated platelets mediate inflammatory signaling by regulated interleukin 1beta synthesis. J Cell Biol 2001; 154: 485-490.
24 Brown GT. et al. Lipopolysaccharide stimulates platelets through an IL-1β autocrine loop. J Immunol 2013; 191: 5196-5203.
25 Hottz ED. et al. Platelets mediate increased endothelium permeability in dengue through NLRP3-inflammasome activation. Blood 2013; 122: 3405-3414.
26 Brown GT, McIntyre TM.. Lipopolysaccharide signaling without a nucleus: kinase cascades stimulate platelet shedding of proinflammatory IL-1β-rich micro-particles. J Immunol 2011; 186: 5489-5496.
27 Simon AY. et al. Dengue virus binding and replication by platelets. Blood 2015; 126: 378-385.
28 Schwertz H. et al. Signal-dependent splicing of tissue factor pre-mRNA modulates the thrombogenecity of human platelets. J Exp Med 2006; 203: 2433-2440.
29 Brogren H. et al. Platelets synthesize large amounts of active plasminogen activator inhibitor 1. Blood 2004; 104: 3943-3948.
30 Nilsson RJA. et al. Blood platelets contain tumor-derived RNA biomarkers. Blood 2011; 118: 3680-3683.
31 Zomer A. et al. In vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior. Cell 2015; 161: 1046-1057.
32 Skog J. et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 2008; 10: 1470-1476.
33 Best MG, Sol N, Kooi I. et al. RNA- Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics. Cancer Cell 2015; 28: 666-676.
34 Schubert S. et al. A tour through the transcriptional landscape of platelets. Blood 2014; 124: 493-502.
35 Bray PF. et al. The complex transcriptional landscape of the anucleate human platelet. BMC Genomics 2013; 14: 1.
36 Eicher JD. et al. Characterisation of the platelet transcriptome by RNA sequencing in patients with acute myocardial infarction. Platelets 2016; 27: 230-239.
37 Stakos DA. et al. Platelet microRNAs: From platelet biology to possible disease biomarkers and therapeutic targets. Platelets 2012; 24: 579-589.
38 Nagalla S. et al. Platelet microRNA-mRNA coexpression profiles correlate with platelet reactivity. Blood 2011; 117: 5189-5197.
39 Plé H. et al The repertoire and features of human platelet microRNAs. PLoS one 2012; 07: e50746.
40 Landry P. et al. Existence of a microRNA pathway in anucleate platelets. Nat Struct Mol Biol 2009; 16: 961-966.
41 Edelstein LC. et al. Racial differences in human platelet PAR4 reactivity reflect expression of PCTP and miR-376c. Nat Med 2013; 19: 1609-1616.
42 Rowley JW. et al. Dicer1 mediated miRNA processing shapes the mRNA profile and function of murine platelets. Blood 2016; 127: 1743-1751.
43 Boilard E. et al. Platelets amplify inflammation in arthritis via collagen-dependent microparticle production. Science 2010; 327: 580-583.
44 Langer HF. et al. Platelets contribute to the pathogenesis of experimental autoimmune encephalomyelitis. Circ Res 2012; 110: 1202-1210.
45 Hu H, Zhu L, Huang Z. et al. Platelets enhance lymphocyte adhesion and infiltration into arterial thrombus. Thromb Haemost 2010; 104: 1184-1192.
46 da Costa Martins PA. et al Platelet binding to monocytes increases the adhesive properties of monocytes by up-regulating the expression and functionality of beta1 and beta2 integrins. J Leuk Biol 2006; 79: 499-507.
47 Santoso S. 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.
48 Wang Y. 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.
49 Seizer P. et al. EMMPRIN (CD147) is a novel receptor for platelet GPVI and mediates platelet rolling via GPVI-EMMPRIN interaction. Thromb Haemost 2009; 101: 682-686.
50 Schulz C. et al. EMMPRIN (CD147/basigin) mediates platelet-monocyte interactions in vivo and augments monocyte recruitment to the vascular wall. J Thromb Haemost 2011; 09: 1007-1019.
51 Schmidt R. et al. Extracellular matrix metalloproteinase inducer (CD147) is a novel receptor on platelets, activates platelets, and augments nuclear factor kappaB-dependent inflammation in monocytes. Circ Res 2008; 102: 302-309.
52 Seizer P. et al. Extracellular cyclophilin A activates platelets via EMMPRIN (CD147) and PI3K/Akt signaling, which promotes platelet adhesion and thrombus formation in vitro and in vivo. Arterioscler Thromb Vasc Biol 2015; 35: 655-663.
53 Postea O. et al. Contribution of platelet CX(3)CR1 to platelet-monocyte complex formation and vascular recruitment during hyperlipidemia. Arterioscler Thromb Vasc Biol 2012; 32: 1186-1193.
54 Langer HF. et al. Platelets recruit human dendritic cells via Mac-1/JAM-C interaction and modulate dendritic cell function in vitro. Arterioscler Thromb Vasc Biol 2007; 27: 1463-1470.
55 Schleicher RI. et al. Platelets induce apoptosis via membrane-bound FasL. Blood 2015; 126: 1483-1493.
56 Massberg S. et al. A critical role of platelet adhesion in the initiation of atherosclerotic lesion formation. J Exp Med 2002; 196: 887-896.
57 Huo Y. et al. Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E. Nat Med 2003; 09: 61-67.
58 Frenette PS. et al. P- Selectin glycoprotein ligand 1 (PSGL-1) is expressed on platelets and can mediate platelet-endothelial interactions in vivo. J Exp Med 2000; 191: 1413-1422.
59 Theilmeier G. et al. Endothelial von Willebrand factor recruits platelets to atherosclerosis-prone sites in response to hypercholesterolemia. Blood 2002; 99: 4486-4493.
60 May AE. et al Engagement of glycoprotein IIb/IIIa (alpha(IIb)beta3) on platelets upregulates CD40L and triggers CD40L-dependent matrix degradation by endothelial cells. Circulation 2002; 106: 2111-2117.
61 Lievens D. et al. Platelet CD40L mediates thrombotic and inflammatory processes in atherosclerosis. Blood 2010; 116: 4317-4327.
62 Gerdes N. et al. Platelet CD40 Exacerbates Atherosclerosis by Transcellular Activation of Endothelial Cells and Leukocytes. Arterioscler Thromb Vasc Biol 2016; 36: 482-490.
63 Weyrich AS. et al. Activated platelets signal chemokine synthesis by human monocytes. J Clin Invest 1996; 97: 1525-1534.
64 Gerdes N. et al. Platelets regulate CD4+ T-cell differentiation via multiple chemokines in humans. Thromb Haemost 2011; 106: 353-362.
65 Tersteeg C. et al. FLow-induced PRotrusions (FLIPRs): a platelet-derived platform for the retrieval of microparticles by monocytes and neutrophils. Circ Res 2014; 114: 780-791.
66 Sadallah S. et al. Microparticles (ectosomes) shed by stored human platelets downregulate macrophages and modify the development of dendritic cells. J Immunol 2011; 186: 6543-6552.
67 Laffont B. et al. Platelet microparticles reprogram macrophage gene expression and function. Thromb Haemost 2016; 115: 311-323.
68 Vasina EM. et al. Microparticles from apoptotic platelets promote resident macrophage differentiation. Cell Death Dis 2011; 02: e211.
69 Clark SR. et al. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med 2007; 13: 463-469.
70 Etulain J. et al. P-selectin promotes neutrophil extracellular trap formation in mice. Blood 2015; 126: 242-246.
71 Maugeri N. et al. Activated platelets present high mobility group box 1 to neutrophils, inducing autophagy and promoting the extrusion of neutrophil extracellular traps. J Thromb Haemost 2014; 12: 2074-2088.
72 Rossaint J. et al. Synchronized integrin engagement and chemokine activation is crucial in neutrophil extracellular trap-mediated sterile inflammation. Blood 2014; 123: 2573-2584.
73 Koenen RR. et al. Disrupting functional interactions between platelet chemokines inhibits atherosclerosis in hyperlipidemic mice. Nat Med 2009; 15: 97-103.
74 Hidalgo A. et al. Heterotypic interactions enabled by polarized neutrophil microdomains mediate thromboinflammatory injury. Nat Med 2009; 15: 384-391.
75 Sreeramkumar V. et al. Neutrophils scan for activated platelets to initiate inflammation. Science 2014; 346: 1234-1238.
76 Niemann S. et al. Soluble fibrin is the main mediator of Staphylococcus aureus adhesion to platelets. Circulation 2004; 110: 193-200.
77 Verschoor A. et al. A platelet-mediated system for shuttling blood-borne bacteria to CD8α+ dendritic cells depends on glycoprotein GPIb and complement C3. Nat Immunol 2011; 12: 1194-1201.
78 Wong CHY. et al. Nucleation of platelets with blood-borne pathogens on Kupffer cells precedes other innate immunity and contributes to bacterial clearance. Nat Immunol 2013; 14: 785-792.
79 Sehgal S, Storrie B.. Evidence that differential packaging of the major platelet granule proteins von Willebrand factor and fibrinogen can support their differential release. J Thromb Haemost 2007; 05: 2009-2016.
80 Chatterjee M. et al. Distinct platelet packaging, release, and surface expression of proangiogenic and antiangiogenic factors on different platelet stimuli. Blood 2011; 117: 3907-3911.
81 Kamykowski J. et al. Quantitative immunofluorescence mapping reveals little functional coclustering of proteins within platelet αα-granules. Blood 2011; 118: 1370-1373.
82 Jonnalagadda D. et al. Platelet secretion is kinetically heterogeneous in an agonist-responsive manner. Blood 2012; 120: 5209-5216.
83 Burkhart JM. et al. The first comprehensive and quantitative analysis of human platelet protein composition allows the comparative analysis of structural and functional pathways. Blood 2012; 120: e73-82.
84 Hundelshausen von P. et al Heterophilic interactions of platelet factor 4 and RANTES promote monocyte arrest on endothelium. Blood 2005; 105: 924-930.
85 Kramp BK. et al. Exchange of extracellular domains of CCR1 and CCR5 reveals confined functions in CCL5-mediated cell recruitment. Thromb Haemost 2013; 110: 795-806.
86 Grommes J. et al. Disruption of platelet-derived chemokine heteromers prevents neutrophil extravasation in acute lung injury. Am J Respir Crit Care Med 2012; 185: 628-636.
87 Alard J-E. et al Recruitment of classical monocytes can be inhibited by disturbing heteromers of neutrophil HNP1 and platelet CCL5. Sci Transl Med 2015; 07 317ra 196-6.
88 Projahn D. et al. Controlled intramyocardial release of engineered chemokines by biodegradable hydrogels as a treatment approach of myocardial infarction. J Cell Mol Med 2014; 18: 790-800.
89 Horn M. et al. Human neutrophil alpha-defensins induce formation of fibrinogen and thrombospondin-1 amyloid-like structures and activate platelets via glycoprotein IIb/IIIa. J Thromb Haemost 2012; 10: 647-661.
90 Quinn KL. et al. Human neutrophil peptides mediate endothelial-monocyte interaction, foam cell formation, and platelet activation. Arterioscler Thromb Vasc Biol 2011; 31: 2070-2079.
91 Linden MD. et al. High platelet reactivity and antiplatelet therapy resistance. Semin Thromb Hemost 2012; 38: 200-212.
92 Naik MU. et al. JAM-A protects from thrombosis by suppressing integrin αIIbβ3-dependent outside-in signaling in platelets. Blood 2012; 119: 3352-3360.
93 Karshovska E. et al. Hyperreactivity of junctional adhesion molecule a-deficient platelets accelerates atherosclerosis in hyperlipidemic mice. Circ Res 2015; 116: 587-599.
94 Willecke F. et al. Interruption of classic CD40L-CD40 signalling but not of the novel CD40L- Mac-1 interaction limits arterial neointima formation in mice. Thromb Haemost 2014; 112: 379-389.
95 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.