The role of platelets in inflammation and immunity
https://doi.org/10.17709/2409-2231-2018-5-3-4
Abstract
In recent decades, significant progress has been made in understanding the mechanisms of platelet function and platelet hemostasis correction. Platelets are considered as the most important participants of both normal, and pathological thrombotic process characteristic of the most different diseases and states. In the present review pathophysiological mechanisms of platelet synthesis of various mediators with paracrine effects, which can influence the function of other cells, are consecrated. The physiology of platelets was considered in detail. The leading role of platelets in pathogenesis of the majority of diseases of cardiovascular system as modulators of inflammatory reactions of the immune response which are considered as the leading mechanism of development of atherosclerosis was shown. The ability of platelets to encode inflammatory proteins allowing them to influence adaptive immunity functions was discussed. The role of platelets as a key component of the innate immune system was presented, which is confirmed by the presence of Tolllike receptors (TLR) and glycoproteins, such as integrin αIIbβ3, glycoprotein Ib-IX and FcγRIIa, involved in interaction with bacterial cells. The pathogenesis of the formation of platelet-leukocyte aggregates due to the rapid reversible interaction of P-selectin (CD62P) on the platelet surface with ligand-1 glycoprotein P-selectin (PSGL-1) on the plasma of leukocytes and the mechanism of extracellular neutrophil traps (NETs), as well as the influence of platelets on the function of lymphocytes was presented. The role of platelets in cancer progression, metastasis and thrombosis is considered, and the interrelation of thrombosis and metastasis in malignant diseases was analyzed. The efficiency of the use of antithrombotic drugs in the prevention of thrombosis and, as a consequence, in the prevention of cardiovascular diseases and cancer was discussed.
About the Authors
S. P. SviridovaRussian Federation
Svetlana P. Sviridova - MD, PhD, DSc, professor, leading researcher of the ICU №1.
24 Kashirskoe sh., Moscow 115478
Competing Interests:
No confl ict of interest
O. V. Somonova
Russian Federation
Oksana V. Somonova - MD, PhD, DSc, leading researcher of the clinical diagnostic laboratory.
24 Kashirskoe sh., Moscow 115478
Competing Interests:
No confl ict of interest
Sh. R. Kashiya
Russian Federation
Shalva R. Kashiya - MD, PhD, head of the department of functional diagnosis, intensive care and rehabilitation.
24 Kashirskoe sh., Moscow 115478
Competing Interests:
No confl ict of interest
O. A. Obukhova
Russian Federation
Olga A. Obukhova - MD, PhD, researcher of the department of functional diagnosis, intensive care and rehabilitation.
24 Kashirskoe sh., Moscow 115478
Competing Interests:
No confl ict of interest
A. V. Sotnikov
Russian Federation
Anatolii V. Sotnikov - MD, PhD, DSc, head of the department of ICU.
10 Priorova str., Moscow 127299
Competing Interests:
No confl ict of interest
References
1. Freedman JE. Molecular regulation of platelet-dependent thrombosis. Circulation. 2005 Oct 25;112(17):2725-34. DOI: 10.1161/CIRCULATIONAHA.104.494468
2. Jenne CN, Urrutia R, Kubes P. Platelets: bridging hemostasis, inflammation, and immunity. Int J Lab Hematol. 2013 Jun;35(3):254-61. DOI: 10.1111/ijlh.12084.
3. Wagner DD, Burger PC. Platelets in inflammation and thrombosis. Arterioscler Thromb Vasc Biol. 2003 Dec;23(12):2131-7. DOI: 10.1161/01.ATV.0000095974.95122.EC
4. Karin M. Nuclear factor-kappa B in cancer development and progression. Nature. 2006 May 25;441(7092):431-6. DOI: 10.1038/nature04870
5. Obukhova OA, Kashiya ShR, Kourmukov IA. Thrombosis prevention in oncogynecology. Oncogynecology. 2013;2:64-72. (In Russian).
6. Meikle CKS, Kelly CA, Garg P, Wuescher LM, Ali RA, Worth RG. Cancer and Thrombosis: The Platelet Perspective. Front Cell Dev Biol. 2017 Jan 5;4:147. DOI: 10.3389/fcell.2016.00147
7. Machlus KR, Italiano JE. The incredible journey: from megakaryocyte development to platelet formation. J Cell Biol. 2013 Jun 10;201(6):785-96. DOI: 10.1083/jcb.201304054
8. Lindemann S, Gawaz M. The active platelet: translation and protein synthesis in an anucleate cell. Semin Thromb Hemost. 2007 Mar;33(2):144-50.
9. Kapur R, Semple JW. Platelets as immune-sensing cells. Blood Adv. 2016 Nov 22;1(1):10-14. DOI: 10.1182/bloodadvances.2016000067
10. Landry P, Plante I, Ouellet DL, Perron MP, Rousseau G, Provost P. Existence of a microRNA pathway in anucleate platelets. Nat Struct Mol Biol. 2009 Sep;16(9):961-6. DOI: 10.1038/nsmb.1651
11. Rosenwald IB, Pechet L, Han A, Lu L, Pihan G, Woda B, et al. Expression of translation initiation factors elF-4E and elF-2alpha and a potential physiologic role of continuous protein synthesis in human platelets. Thromb Haemost. 2001 Jan;85(1):142-51.
12. Zimmerman GA, Weyrich AS. Signal-Dependent Protein Synthesis by Activated Platelets New Pathways to Altered Phenotype and Function. Arterioscler Thromb Vasc Biol. 2008 Mar;28(3):s17-24. DOI: 10.1161/ATVBAHA.107.160218.
13. Solpov AV. Thrombocyte-leukocyte adhesion in norm and pathology. Dissertation. Chita, 2015, 233 p. (In Russian).
14. Leslie M. Cell biology. Beyond clotting: the powers of platelets. Science. 2010 Apr 30;328(5978):562-4. DOI: 10.1126/science.328.5978.562.
15. Heemskerk JW, Mattheij NJ, Cosemans JM. Platelet-based coagulation: different populations, different functions. J Thromb Haemost. 2013 Jan;11(1):2-16. DOI: 10.1111/jth.12045
16. Fox JE. Cytoskeletal proteins and platelet signaling. Thromb Haemost. 2001 Jul;86(1):198-213.
17. Kral JB, Schrottmaier WC, Salzmann M, Assinger A. Platelet Interaction with Innate Immune Cells. Transfus Med Hemother. 2016 Mar;43(2):78-88. DOI: 10.1159/000444807.
18. Yakimenko AO, Verholomova FY, Kotova YN, Ataullakhanov FI, Panteleev MA. Identification of different proaggregatory abilities of activated platelet subpopulations. Biophys J. 2012 May 16;102(10):2261-9. DOI: 10.1016/j.bpj.2012.04.004.
19. Lindemann S, Kraemer B, Daub K, Stellos K, Gawaz M. Molecular pathways used by platelets to initiate and accelerate atherogenesis. Curr Opin Lipidol. 2007 Oct;18(5):566-73. DOI: 10.1097/ MOL.0b013e3282ef7c1e
20. Weyrich AS, Lindemann S, Tolley ND, Kraiss LW, Dixon DA, Mahoney TM, et al. Change in protein phenotype without a nucleus: translational control in platelets. Semin Thromb Hemost. 2004 Aug;30(4):491-8. DOI: 10.1055/s-2004-833484
21. Golebiewska EM, Alastair W. Poole Platelet secretion: From haemostasis to wound healing and beyond. Blood Rev. 2015 May;29(3):153-62. DOI: 10.1016/j.blre.2014.10.003
22. McNicol A, Israels SJ. Beyond hemostasis: the role of platelets in inflammation, malignancy and infection. Cardiovasc Hematol Disord Drug Targets. 2008 Jun;8(2):99-117.
23. Weyrich AS, Zimmerman GA. Platelets: signaling cells in the immune continuum. Trends Immunol. 2004 Sep;25(9):489-95. DOI: 10.1016/j.it.2004.07.003
24. Li Z, Yang F, Dunn S, Gross AK, Smyth SS. Platelets as immune mediators: their role in host defense responses and sepsis. Thromb Res. 2011 Mar;127(3):184-8. DOI: 10.1016/j.thromres.2010.10.010
25. Stark RJ, Aghakasiri N, Rumbaut RE. Platelet-derived Tolllike receptor 4 (Tlr-4) is sufficient to promote microvascular thrombosis in endotoxemia. PLoS One. 2012;7(7):e41254. DOI: 10.1371/journal.pone.0041254
26. Tang YQ, Yeaman MR, Selsted ME. Antimicrobial peptides from human platelets. Infect Immun. 2002 Dec;70(12):6524-33.
27. Kerrigan SW, Cox D. Platelet-bacterial interactions. Cell Mol Life Sci. 2010 Feb;67(4):513-23. DOI: 10.1007/s00018-0090207-z
28. Andonegui G, Kerfoot SM, McNagny K, Ebbert KV, Patel KD, Kubes P. Platelets express functional Toll-like receptor-4. Blood. 2005 Oct 1;106(7):2417-23. DOI: 10.1182/blood-2005-03-0916
29. Gleissner CA, von Hundelshausen P, Ley K. Platelet chemokines in vascular disease. Arterioscler Thromb Vasc Biol. 2008 Nov;28(11):1920-7. DOI: 10.1161/ATVBAHA.108.169417.
30. Hurley SM, Kahn F, Nordenfelt P, Morgelin M, Sorensen OE, Shannon O. Platelet-dependent neutrophil function is dysregulated by m protein from Streptococcus pyogenes. Infect Immun. 2015 Sep;83(9):3515-25. DOI: 10.1128/IAI.00508-15.
31. Yeaman MR. Platelets: at the nexus of antimicrobial defence. Nat Rev Microbiol. 2014 Jun;12(6):426-37. DOI: 10.1038/nrmicro3269
32. Fujimi S, Mac Conmara PM, Maung AA, Yan Zang, Mannick JA, Lederer JA, et al. Platelet depletion in mice increases mortality after thermal injury. Blood. 2006 Jun 1;107(11):4399-406. DOI: 10.1182/blood-2005-09-3776
33. Li N. Platelet– lymphocyte cross–talk. J Leukoc Biol. 2008 May;83(5):1069-78. DOI: 10.1189/jlb.0907615.
34. Elgueta R, Benson MJ, de Vries VC, Wasiuk A, Guo Y, Noelle RJ. Molecular mechanism and function of CD40/CD40L engagement in the immune system. Immunol Rev. 2009 May;229(1):152-72. DOI: 10.1111/j.1600-065X.2009.00782.x.
35. Yacoub D, Hachem A, Théorêt JF, Gillis MA, Mourad W, Merhi Y. Enhanced levels of soluble CD40 ligand exacerbate platelet aggregation and thrombus formation through a CD40-dependent tumor necrosis factor receptor-associated factor-2/Rac1/p38 mitogen-activated protein kinase signaling pathway. Arterioscler Thromb Vasc Biol. 2010 Dec;30(12):2424-33. DOI: 10.1161/ATVBAHA.110.216143
36. Brinkmann V, Rechard U, Goosmann C. Neutrophil extracelllulartraps kill bacteria. Science. 2004 Mar 5;303(5663):1532-5. DOI: 10.1126/science.1092385
37. Sinauridze EI, Kireev DA, Popenko NY, Pichugin AV, Panteleev MA, Krymskaya OV, et al. Platelet microparticle membranes have 50to 100 fold higher specific procoagulant activity than activated platelets. Thromb Haemost. 2007 Mar;97(3):425-34.
38. De Maat S, Maas C. Factor XII: form determines function. J Thromb Haemost. 2016 Aug;14(8):1498-506. DOI: 10.1111/jth.13383.
39. Owens AP, Mackman N. Microparticles in hemostasis and thrombosis. Circ Res. 2011 May 13;108(10):1284-97. DOI: 10.1161/CIRCRESAHA.110.233056.
40. Fuchs TA, Brill A, Duerschmied D, Schatzberg D, Monestier M, Myers DD Jr, et al. Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15880-5. DOI: 10.1073/pnas.1005743107.
41. Obukhova O, Kashiya S, Kurmukov I. Metabolic Disorders in Patients with Advanced Gastric Cancer before Antitumor Chemotherapy. Clinical Nutrition. 2017;36:216.
42. Hottz ED, Medeiros-de-Moraes IM, Vieira-de-Abreu A, de Assis EF, Vals-de-Souza R, Castro-Faria-Neto HC, et al. Platelet activation and apoptosis modulate monocyte inflammatory responses in dengue. J Immunol. 2014 Aug 15;193(4):1864-72. DOI: 10.4049/jimmunol.1400091
43. Badrnya S, Schrottmaier WC, Kral JB, Yaiw KC, Volf I, Schabbauer G, et al. Platelets mediate oxidized low-density lipoprotein-induced monocyte extravasation and foam cell formation. Arterioscler Thromb Vasc Biol. 2014 Mar;34(3):571-80. DOI: 10.1161/ATVBAHA.113.302919
44. Maloney SF, Brass LF, Diamond SL. P2Y12 or P2Y1 inhibitors reduce platelet depositionin a microfluidic model of thrombosis while apyrase lacks efficacy under flow conditions. Integr Biol (Camb). 2010 Apr;2(4):183-92. DOI: 10.1039/b919728a
45. Mickelson JK, Lakkis NM, Villarreal-Levy G, Hughes BJ, Smith CW. Leukocyte activation with platelet adhesion after coronary angioplasty: a mechanism for recurrent disease? J Am Coll Cardiol. 1996 Aug;28(2):345-53. DOI: 10.1016/0735-1097(96)00164-7
46. Roxburgh CS, McMillan DC. Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. Future Oncol. 2010 Jan;6(1):149-63. DOI: 10.2217/fon.09.136
47. Vitkovsky YuA, Kuznick ВI, Solpov AN. Pathogeneticsignificance of lymphocyte-to-platelet adherence. Medical Immunology. 2006;8(5-6):745-53. (In Russian).
48. Ozawa T, Ishihara S, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, et al. The preoperative platelet to lymphocyte ratio is a prognostic marker in patients with stage II colorectal cancer. Int J Colorectal Dis. 2015 Sep;30(9):1165-71. DOI: 10.1007/s00384-015-2276-9.
49. Zhao QT, Yuan Z, Zhang H, Zhang XP, Wang HE, Wang ZK, et al. Prognostic role of platelet to lymphocyte ratio in non-small cell lung cancers: a meta-analysis including 3,720 patients. Int J Cancer. 2016 Jul 1;139(1):164-70. DOI: 10.1002/ijc.30060
50. Bhatti I, Peacock O, Lloyd G, Larvin M, Hall RI. Preoperative hematologic markers as independent predictors of prognosis in resected pancreatic ductal adenocarcinoma: neutrophil-lymphocyte versus platelet-lymphocyte ratio. Am J Surg. 2010 Aug;200(2):197-203. DOI: 10.1016/j.amjsurg.2009.08.041.
51. Lian L, Xia YY, Zhou C, Shen XM, Li XL, Han SG, et al. Application of platelet/lymphocyte and neutrophil/lymphocyte ratios in early diagnosis and prognostic prediction in patients with resectable gastric cancer. Cancer Biomark. 2015;15(6):899-907. DOI: 10.3233/CBM-150534
52. Xiaobin Gu, Xian-Shu Gao, Ming Cui, Mu Xie, Chuan Peng, Yun Bai, et al. Clinico-pathological and prognostic significance of platelet to lymphocyte ratio in patients with gastric cancer. Oncotarget. 2016 Nov 1;7(44):72276-72289. DOI: 10.18632/oncotarget.10848
53. Templeton AJ, Ace O, McNamara MG, Al-Mubarak M, Vera-Badillo FE, Hermanns T, et al. Prognostic role of platelet to lymphocyte ratio in solid tumors: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2014 Jul;23(7):1204-12. DOI: 10.1158/1055-9965.EPI-14-0146
54. Kara M, Uysal S, Altinişik U, Cevizci S, Güçlü O, Dereköy FS. The pre-treatment neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and red cell distribution width predict prognosis in patients with laryngeal carcinoma. Eur Arch Otorhinolaryngol. 2017 Jan;274(1):535-542. DOI: 10.1007/s00405-016-4250-8
55. Koenig-Oberhuber V, Filipovic M. New antiplatelet drugs and new oral anticoagulants. Br J Anaesth. 2016 Sep;117 Suppl 2:ii74ii84. DOI: 10.1093/bja/aew214.
56. Solpov A, Shenkman B, Vitkovsky Y, Brill G, Koltakov A, Farzam N, et al. Platelets enhance CD4+ lymphocyte adhesion to extracellular matrix under flow conditions: Role of platelet aggregation, integrins, and non– integrin receptors. Thromb Haemost. 2006 May;95(5):815-21.
57. Ueno M, Kodali M, Tello-Montoliu A, Angiolillo DJ. Role of platelets and antiplatelet therapy in cardiovascular disease. J Atheroscler Thromb. 2011;18(6):431-42.
58. Sutcliffe P, Connock M, Gurung T, Freeman K, Johnson S, Kandala NB, et al. Aspirin for prophylactic use in the primary prevention of cardiovascular disease and cancer: a systematic review and overview of reviews. Health Technol Assess. 2013 Sep;17(43):1-253. DOI: 10.3310/hta17430.
59. Harris RE, Beebe-Donk J, Doss H, Doss DB. Aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs in cancer prevention: a critical review of non-selective COX-2 blockade (review). Oncol Rep. 2005 Apr;13(4):559-83.
60. Cooke NM, Spillane CD, Shils O, O’Leary J, Kenny D. Aspirin and P2Y12 inhibition attenuate platelet-induced ovarian cancer cell invasion. BMC Cancer. 2015 Sep 9;15:627. DOI: 10.1186/s12885-015-1634-x.
Review
For citations:
Sviridova S.P., Somonova O.V., Kashiya Sh.R., Obukhova O.A., Sotnikov A.V. The role of platelets in inflammation and immunity. Research and Practical Medicine Journal. 2018;5(3):40-52. (In Russ.) https://doi.org/10.17709/2409-2231-2018-5-3-4