ТРОМБОЦИТЫ КАК АКТИВАТОРЫ И РЕГУЛЯТОРЫ ВОСПАЛИТЕЛЬНЫХ И ИММУННЫХ РЕАКЦИЙ. ЧАСТЬ 2. ТРОМБОЦИТЫ КАК УЧАСТНИКИ ИММУННЫХ РЕАКЦИЙ

Тромбоцитам принадлежит ведущая роль в сопряжении тромбоза, воспаления и врожденных иммунных реакций. Тромбоциты устанавливают стабильное адгезионное взаимодействие с иммунными клетками. Активированные тромбоциты экспрессируют CD40L (CD154), мембранный гликопротеин семейства фактора некроза опухоли (TNF), причем тромбоциты представляют собой главный источник sCD40L в плазме крови. Тромбоцитарный CD154 может взаимодействовать с рецептором CD40 на эндотелии, вызывая воспалительный ответ, и В-лимфоцитах, усиливая продукцию ими иммуноглобулинов. CD154 тромбоцитов в комплексе с другими сигналами может вызвать созревание и активацию дендритных клеток (ДК). Тромбоциты обладают функциональными рецепторами TLR2, TLR4, TLR7 и TLR9. На тромбоцитах присутствуют Fc-рецепторы, в том числе FcγRIIA, FcεRI и FcαRIA. FcγRIIA на тромбоцитах может вовлекать их в защиту от бактерий. Перекрестная связь FcαRI на тромбоцитах приводит к продукции ими протромботических и провоспалительных медиаторов, таких как тканевой фактор и IL-1β. Активация тромбоцитов через FcεR1 вызывает высвобождение хемокина RANTES и серотонина, которые способствуют провоспалительному ответу других иммунных клеток. Тромбоциты обладают рецепторами для активированных компонентов комплемента (CR2, CR3, CR4, C1qR) и C1-ингибитора, факторов D и H. Активированные тромбоциты способствуют активации системы комплемента через высвобождение протеинкиназ и ATФ, а также путем фосфорилирования C3 и C3b. В α-гранулах тромбоцитов хранятся хемокины, которые представляют и самую многочисленную группу антимикробных белков тромбоцитов (киноцидины), а в цитоплазме тромбоцитов имеется антимикробный белок семейства дефензинов – hBD-1. Продуктами тромбоцитов, относящимися к семейству цитокинов и их рецепторов, признаны лиганд и рецептор суперсемейства TNF (TRAIL и LIGHT), хемокин SDF-1 (CXCL12), интерлейкины IL-1β, IL-8 и растворимый рецептор IL-6 (sRIL-6). Белок HMGB-1, классифицированный как воспалительный цитокин, экспрессируется в активированных тромбоцитах и вызывает формирование нейтрофилами внеклеточных ловушек. Тромбоциты являются источником многочисленных факторов роста, включая EGF-α и EGF-β1, EGF-β2, TGF-α и TGF-β1, TGF-β2, PDGF, HGF, FGF-β, IGF, про и антиангиогенные факторы, например VEGF-F и ангиопоэтины Ang-1 и Ang-2. Реализация иммунных функций тромбоцитов осуществляется при их взаимодействии с лейкоцитами, которые привлекаются к месту инфекции и воспаления и удерживаются при формировании «иммунного тромба» в условиях высокого напряжения сдвига. Тромбоциты могут не только поддерживать и направлять иммунный ответ, но и инициировать его. Они способны презентировать антиген в контексте молекул MHC I класса и активировать наивные CD8⁺Т-лимфоциты. В обзоре рассмотрены некоторые последствия взаимодействия тромбоцитов с нейтрофилами, моноцитами, дендритными клетками и лимфоцитами.

1. Серебряная Н.Б., Шанин С.Н., Фомичева Е.Е., Якуцени П.П. Тромбоциты как активаторы и регуляторы воспалительных и иммунных реакций. Часть 1. Основные характеристики тромбоцитов как воспа-лительных клеток// Медицинская иммунология, 2018. Т. 20, № 6. С. 785-796. [Serebryanaya N.B., Shanin S.N., Fomicheva E.E., Yakutseni P.P. Blood platelets as activators and regulators of inflammatory and immune reactions. Part 1. Basic characteristics of platelets as inflammatory cells. Meditsinskaya immunologiya = Medical Immunology (Russia), 2018, Vol. 20, no. 6, pp. 785-796.(In Russ.)] doi: 10.15789/1563-0625-2018-6-785-796.

2. Andonegui G., Kerfoot S.M., McNagny K., Ebbert K.V.J., Patel K.D., Kubes P. Platelets express functional Toll-like receptor-4. Blood, 2005, Vol. 106, pp. 2417-2423.

3. Andrews R.K., Arthur J.F., Gardiner E. Neutrophil extracellular traps (NETs) and the role of platelets in infection. Thromb. Haemost., 2014, Vol. 112, no. 4, pp. 659-665.

4. Anitua E., Andia I., Ardanza B., Nurden P., Nurden A.T. Autologous platelets as a source of proteins for healing and tissue regeneration. Thromb. Haemost., 2004, Vol. 91, pp. 4-15.

5. Arisato T., Hashiguchi T., Sarker K.P., Arimura K., Asano M., Matsuo K., Osame M., Maruyama I. Highly accumulated platelet vascular endothelial growth factor in coagulant thrombotic region.J. Thromb. Haemost., 2003, no. 1, pp. 2589-2593.

6. Blair P., Flaumenhaft R. Platelet α-granules: Basic biology and clinical correlates. Blood Rev., 2009, Vol. 23, no. 4, pp. 177-189.

7. Boehlen F., Clemetson K.J. Platelet chemokines and their receptors: what is their relevance to platelet storage and transfusion practice?Transfus. Med., 2001, no. 11, pp. 403-417.

8. Brandt E., Petersen F., Ludwig A., Ehlert J.E., Bock L., Flad H.D. The beta-thromboglobulins and platelet factor 4: blood platelet-derived CXC chemokines with divergent roles in early neutrophil regulation. J. Leukoc. Biol., 2000, Vol. 67, pp. 471-478.

9. Brill A., Elinav H., Varon D. Differential role of platelet granular mediators in angiogenesis. Cardiovasc. Res., 2004, Vol. 63, pp. 226-235.

10. Chapman L.M., Aggrey A.A., Field D.J., Srivastava K., Ture S., Yui K., Topham D.J., Baldwin W.M. 3rd , Morrell C.N. Platelets present antigen in the context of MHC class I. J. Immunol., 2012, Vol. 189, no. 2, pp. 916-923.

11. Clark S.R., Ma A.C., Tavener S.A., Mcdonald B., Goodarzi Z., Kelly M.M., Patel K.D., Chakrabarti S., Mcavoy E., Sinclair G.D., Keys E.M., Allen-Vercoe E., Devinney R., Doig C.J., Green F.H.Y., Kubes P. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat. Med., 2007, Vol. 13, pp. 463-469.

12. Cognasse F., Hamzeh H., Chavarin P., Acquart S., Genin C., Garraud O. Evidence of Toll-like receptor molecules on human platelets. Immunol. Cell. Biol., 2005, Vol. 83, pp. 196-198.

13. Cognasse F., Hamzeh-Cognasse H., Lafarge S., Chavarin P., Cogné M., Richard Y., Garraud O. Human platelets can activate peripheral blood B cells and increase production of immunoglobulins. Exp. Hematol., 2007, Vol. 35, pp. 1376-1387.

14. Colotta F., Sciacca F.L., Sironi M., Luini W., Rabiet M.J., Mantovani A. Expression of monocyte chemotactic protein-1 by monocytes and endothelial cells exposed to thrombin. Am. J. Pathol., 1994, Vol. 144, no. 5, pp. 975-985.

15. Corken A., Russell S., Dent J., Post S.R., Ware J. Platelet glycoprotein Ib-IX as a regulator of systemic inflammation. Arterioscler. Thromb. Vasc. Biol., 2014, Vol. 34, pp. 996-1001.

16. Danese S., de la Motte C., Reyes B.M., Sans M., Levine A.D., Fiocchi C. Cutting edge: T cells trigger CD40-dependent platelet activation and granular RANTES release: a novel pathway for immune response amplification. J. Immunol., 2004, Vol. 172, pp. 2011-2015.

17. del Conde I., Crúz M.A., Zhang H., López J.A., Afshar-Kharghan V. Platelet activation leads to activation and propagation of the complement system.J. Exp. Med., 2005, Vol. 201, no. 6, pp. 871-879.

18. Delaney M.K., Kim K., Estevez B., Xu Z., Stojanovic-Terpo A., Shen B., Ushio-Fukai M., Cho J., Du X. Differential roles of the NADPH-oxidase 1 and 2 in platelet activation and thrombosis. Arterioscler. Thromb. Vasc. Biol., 2016, Vol. 36, no. 5, pp. 846-854.

19. Diacovo T.G., Catalina M.D., Siegelman M.H., von Andrian U.H. Circulating activated platelets reconstitute lymphocyte homing and immunity in L-selectin-deficient mice. J. Exp. Med., 1998, Vol. 187, no. 2, pp. 197-204.

20. Diacovo T.G., de Fougerolles A.R., Bainton D.F., Springer T.A. A functional integrin ligand on the surface of platelets: intercellular adhesion molecule-2.J. Clin. Invest., 1994, Vol. 94, pp. 1243-1251.

21. Dixon D.A., Tolley N.D., Bemis-Standoli K., Martinez M.L., Weyrich A.S., Morrow J.D., Prescott S.M., Zimmerman G.A. Expression of COX-2 in platelet-monocyte interactions occurs via combinatorial regulation involving adhesion and cytokine signaling.J. Clin. Invest., 2006, Vol. 116, pp. 2727-2738.

22. Duffau P., Seneschal J., Nicco C., Richez C., Lazaro E., Douchet I., Bordes C., Viallard J.-F., Goulvestre C., Pellegrin J.-L., Weil B., Moreau J.-F., Batteux F., Blanco P. Platelet CD154 potentiates interferon-alpha secretion by plasmacytoid dendritic cells in systemic lupus erythematosus.Sci. Transl. Med., 2010, Vol. 1, no. 2 (47), 47ra63. doi: 10.1126/scitranslmed.3001001.

23. Ekdahl K.N., Nilsson B. Phosphorylation of complement component C3 and C3 fragments by a human platelet protein kinase. Inhibition of factor I-mediated cleavage of C3b. J. Immunol., 1995, Vol. 154, no. 12, pp. 6502-6510.

24. Elzey B.D., Ratliff T.L., Sowa J.M., Crist S.A. Platelet CD40L at the interface of adaptive immunity. Thromb. Res., 2011, Vol. 127, no. 3, pp. 180-183.

25. Elzey B.D., Sprague D.L., Ratliff T.L. The emerging role of platelets in adaptive immunity. Cell Immunol., 2005, Vol. 238, pp. 1-9.

26. Evangelista V., Manarini S., Dell’Elba G., Martelli N., Napoleone E., Di S.A., Lorenzet P.S. Clopidogrel inhibits platelet-leukocyte adhesion and platelet-dependent leukocyte activation. Thromb. Haemost., 2005, Vol. 94, no. 3, pp. 568-577.

27. Fleischer J., Grage-Griebenow E., Kasper B., Heine H., Ernst M., Brandt E., Flad H.-D., Petersen F. Platelet factor 4 inhibits proliferation and cytokine release of activated human T cells. J. Immunol., 2002, Vol. 169, pp. 770-777.

28. Foy T.M., Aruffo A., Bajorath J., Buhlmann J.E., Noelle R.J. Immune regulation by CD40 and its ligand GP39. Annu. Rev. Immunol., 1996, Vol. 14, pp. 591-617.

29. Gear A.R.L., Camerini D. Platelet chemokines and chemokine receptors: linking hemostasis, inflammation, and host defense. Microcirculation, 2003, no. 10, pp. 335-350.

30. Gerdes N., Zhu L., Ersoy M., Hermansson A., Hjemdahl P., Hu H., Hansson G.K., Li N. Platelets regulate CD4+ T-cell differentiation viamultiple chemokines in humans. Thromb. Haemost., 2011, Vol. 106, pp. 353-362.

31. Gudbrandsdottir S., Hasselbalch H.C., Nielsen C.H. Activated platelets enhance IL-10 secretion and reduce TNF-αsecretion by monocytes. J. Immunol., 2013, Vol. 191, no. 8, pp. 4059-4067.

32. Hagihara M., Higuchi A., Tamura N., Ueda Y., Hirabayashi K., Ikeda Y., Kato S., Sakamoto S., Hotta T., Handa S., Goto S. Platelets, after exposure to a high shear stress, induce IL-10-producing, mature dendritic cells in vitro. J. Immunol., 2004, Vol. 172, no. 9, pp. 5297-5303.

33. Halvorsen B., Smedbakken L.M., Michelsen A.E., Skjelland M., Bjerkeli V., Sagen E.L., Taskén K., Bendz B., Gullestad L., Holm S., Biessen E.A., Aukrust P. Activated platelets promote increased monocyte expression of CXCR5 through prostaglandin E2-related mechanisms and enhance the anti-inflammatory effects of CXCL13. Atherosclerosis, 2014, Vol. 234, no. 2, pp. 352-359.

34. Hamzeh-Cognasse H., Cognasse F., Palle S., Chavarin P., Olivier T., Delézay O., Pozzetto B., Garraud O. Direct contact of platelets and their released products exert different effects on human dendritic cell maturation. BMC Immunol., 2008, Vol. 9, no. 1, pp. 54-60.

35. Hartwig H., Drechsler M., Lievens D., Kramp B., von Hundelshausen P., Lutgens E., Weber C., Döring Y., Soehnlein O. Platelet-derived PF4 reduces neutrophil apoptosis following arterial occlusion. Thromb. Haemost., 2014, Vol. 111, no. 3, pp. 562-564.

36. Hasegawa S., Pawankar R., Suzuki K., Nakahata T., Furukawa S., Okumura K., Ra C. Functional expression of the high affinity receptor for IgE (FcepsilonRI) in human platelets and its’ intracellular expression in human megakaryocytes. Blood, 1999, Vol. 93, pp. 2543-2551.

37. Hawrylowicz C.M., Howells G.L., Feldmann M. Platelet-derived interleukin 1 induces human endothelial adhesion molecule expression and cytokine production.J. Exp. Med., 1991, Vol. 174, pp. 785-790.

38. Henn V., Slupsky J.R., Gräfe M., Anagnostopoulos I., Förster R., Müller-Berghaus G., Kroczek R.A. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature, 1998, Vol. 391, pp. 591-594.

39. Herter J.M., Rossaint J., Zarbock A. Platelets in inflammation and immunity. J. Thromb. Haemost., 2014, Vol. 12, no. 11, pp. 1764-1775.

40. von Hundelshausen P., Weber K.S., Huo Y., Proudfoot A.E., Nelson P.J., Ley K., Weber C. RANTES deposition by platelets triggers monocyte arrest on inflamed and atherosclerotic endothelium. Circulation, 2001, Vol. 103, pp. 1772-1777.

41. Iannacone M., Sitia G., Isogawa M., Marchese P., Castro M.G., Lowenstein P.R., Chisari F.V., Ruggeri Z.M., Guidotti L.G. Platelets mediate cytotoxic T lymphocyte-induced liver damage. Nat. Med., 2005, no. 11, pp. 1167-1170.

42. Joseph M., Auriault C., Capron A., Vorng H., Viens P. A new function for platelets: IgE-dependent killing of schistosomes. Nature, 1983, Vol. 303, pp. 810-812.

43. Kameyoshi Y., Schröder J.M., Christophers E., Yamamoto S. Identification of the cytokine RANTES released from platelets as an eosinophil chemotactic factor. Int. Arch. Allergy Immunol., 1994, Vol. 104, no. 1, pp. 49-51.

44. Kaneider N.C., Kaser A., Tilg H., Ricevuti G., Wiedermann C.J. CD40 ligand-dependent maturation of human monocyte-derived dendritic cells by activated platelets. Int. J. Immunopathol. Pharmacol., 2003, Vol. 16, pp. 225-231.

45. Katsounas A., Schlaak J.F., Lempicki R.A. CCL5: a double-edged sword in host defense against the hepatitis C virus. Int. Rev. Immunol., 2011, Vol. 30, no. 5-6, pp. 366-378.

46. Kerrigan A.M., Navarro-Nuñez L., Pyz E., Finney B.A., Willment J.A., Watson S.P., Brown G.D. Podoplaninexpressing inflammatory macrophages activate murine platelets via CLEC-2. J. Thromb. Haemost., 2012, no. 10, pp. 484-486.

47. Kim K., Li J., Tseng A., Andrews R.K., Cho J. NOX2 is critical for heterotypic neutrophil-platelet interactions during vascular inflammation. Blood, 2015, Vol. 126, no. 16, pp. 1952-1964.

48. Kissel K., Berber S., Nockher A., Santoso S., Bein G., Hackstein H. Human platelets target dendritic cell differentiation and production of proinflammatory cytokines.Transfusion, 2006, Vol. 46, pp. 818-827.

49. Koupenova M., Vitseva O., MacKay C.R., Beaulieu L.M., Benjamin E.J., Mick E., Kurt-Jones E.A., Ravid K., Freedman J.E. Platelet-TLR7 mediates host survival and platelet count during viral infection in the absence of platelet-dependent thrombosis. Blood, 2014, Vol. 124, pp. 791-802.

50. Kraemer B.F., Campbell R.A., Schwertz H., Cody M.J., Franks Z., Tolley N.D., Kahr W.H., Lindemann S., Seizer P., Yost C.C., Zimmerman G.A., Weyrich A.S. Novel anti-bacterial activities of β-defensin 1 in human platelets: suppression of pathogen growth and signaling of neutrophil extracellular trap formation. PLoS Pathog., 2011, Vol. 7, no. 11, e1002355. doi:10.1371/journal.ppat.1002355.

51. Krotz F., Sohn H.Y., Pohl U. Reactive oxygen species: players in the platelet game. Arterioscler. Thromb. Vasc. Biol., 2004, Vol. 24, no. 11, pp. 1988-1996.

52. Langer H.F., Daub K., Braun G., Schönberger T., May A.E., Schaller M., Stein G.M., Stellos K., Bueltmann A., Siegel-Axel D., Wendel H.P., Aebert H., Roecken M., Seizer P., Santoso S., Wesselborg S., Brossart P., Gawaz M. Platelets recruit human dendritic cells viaMac-1/JAM-C interaction and modulate dendritic cell function in vitro. Arterioscler. Thromb. Vasc. Biol., 2007, Vol. 27, no. 6, pp. 1463-1470.

53. Larsen E., Celi A., Gilbert G.E., Furie B.C., Erban J.K., Bonfanti R., Wagner D.D., Furie B. PADGEM protein: a receptor that mediates the interaction of activated platelets with neutrophils and monocytes.Cell, 1989, Vol. 59, pp. 305-312.

54. León-Ponte M., Ahern G.P., O’Connell P.J. Serotonin provides an accessory signal to enhance T-cell activation by signaling through the 5-HT7 receptor. Blood, 2007, Vol. 109, no. 8, pp. 3139-3146.

55. Li G., Kim Y.J., Mantel C., Broxmeyer H.E. P-selectin enhances generation of CD14 + CD16+ dendritic-like cells and inhibits macrophage maturation from human peripheral blood monocytes.J. Immunol., 2003, Vol. 171, pp. 669-677.

56. Li N. Platelet-lymphocyte cross-talk.J. Leukoc. Biol., 2008, Vol. 83, pp. 1069-1078.

57. Li Zh., Yang F., Dunn S., A. Gross K., Smyth S.S. Platelets as immune mediators: Their role in host defense responses and sepsis.Thromb. Res., 2011, Vol. 127, no. 3, pp. 184-188.

58. Liu C.Y., Battaglia M., Lee S.H., Sun Q-H., Aster R.H., Visentin G.P. Platelet factor 4 differentially modulates CD4+ CD25+ (Regulatory) versus CD4 + CD25-(Nonregulatory) T cells. J. Immunol., 2005, Vol. 174, pp. 2680-2686.

59. Loppnow H., Bil R., Hirt S., Schonbeck U., Herzberg M., Werdan K., Rietschel E.T., Brandt E., Flad H.D. Platelet-derived interleukin-1 induces cytokine production, but not proliferation of human vascular smooth muscle cells. Blood, 1998, Vol. 91, pp. 134-141.

60. Matsuda H., Ushio H., Geba G.P., Askenase P.W. Human platelets can initiate Tcell-dependent contact sensitivity through local serotonin release mediated by IgE antibodies.J. Immunol., 1997, Vol. 158, pp. 2891-2897.

61. Maugeri N., Rovere-Querini P., Evangelista V., Covino C., Capobianco A., Bertilaccio M.T., Piccoli A., Totani L., Cianflone D., Maseri A., Manfredi A.A. Neutrophils phagocytose activated platelets in vivo: a phosphatidylserine, P-selectin, and (beta)2 integrin-dependent cell clearance program. Blood, 2009, Vol. 113, no. 21, pp. 5254-5265.

62. Mei J., Liu Y., Dai N., Favara M., Greene T., Jeyaseelan S., Poncz M., Lee J.S., Worthen G.S. CXCL5 regulates chemokine scavenging and pulmonary host defense to bacterial infection. Immunity, 2010, Vol. 33, pp. 106-117.

63. Michetti N., Weyrich A.S., Zimmerman G.A. Platelet-leukocyte interactions in inflammation and thrombosis. US Hematology, 2009, no. 2, pp. 24-27.

64. Nakanishi T., Inaba M., Inagaki-Katashiba N., Tanaka A., Vien P.T.X., Kibata K., Ito T., Nomura S. Plateletderived RANK ligand enhances CCL17 secretion from dendritic cells mediated by thymic stromal lymphopoietin. Platelets, 2014, Vol. 25, pp. 425-431.

65. Nomura S., Fujita S., Nakanishi T., Yokoi T., Shimamoto K., Miyamoto R., Ito T. Platelet-derived microparticles cause CD154-dependent activation of dendritic cells. Platelets, 2012, Vol. 23, no. 1, pp. 81-82.

66. Nurden A.T., Nurden P., Sanchez M., Andia I., Anitua E. Platelets and wound healing. Front. Biosci., 2008, Vol. 13, pp. 3532-3548.

67. O’Brien M. The reciprocal relationship between inflammation and coagulation. Top Companion Anim. Med., 2012, Vol. 27, no. 2, pp. 46-52.

68. Page C., Pitchford S. Neutrophil and platelet complexes and their relevance to neutrophil recruitment and activation. Int. Immunopharmacol., 2013, Vol. 17, no. 4, pp. 1176-1184.

69. Passacquale G., Vamadevan P., Pereira L., Hamid C., Corrigall V., Ferro A. Monocyte-platelet interaction induces a pro-inflammatory phenotype in circulating monocytes. PLoS ONE, 2011, Vol. 6, no. 10, e25595. doi: 10.1371/journal.pone.0025595.

70. Peerschke E.I., Yin W., Ghebrehiwet B. Сomplement activation on platelets: implications for vascular inflammation and thrombosis. Mol. Immunol., 2010, Vol. 47, no. 13, pp. 2170-2175.

71. Peerschke E.I., Yin W., Grigg S.E., Ghebrehiwet B. Blood platelets activate the classical pathway of human complement. J. Thromb. Haemost., 2006, Vol. 4, no. 9, pp. 2035-2042.

72. Petrucci G., de Cristofaro R., Rutella S., Ranelletti F.O., Pocaterra D., Lancellotti S., Habib A., Patrono C., Rocca B. Prostaglandin E2 differentially modulates human platelet function through the prostanoid EP2 and EP3 receptors. J. Pharmacol. Exp. Ther., 2011, Vol. 336, pp. 391-402.

73. Pintucci G., Froum S., Pinnell J., Mignatti P., Rafii S., Green D. Trophic effects of platelets on cultured endothelial cells are mediated by platelet-associated fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF).Thromb. Haemost., 2002, Vol. 88, pp. 834-842.

74. Qian K., Xie F., Gibson A.W., Edberg J.C., Kimberly R.P., Wu J. Functional expression of IgA receptor FcalphaRI on human platelets. J. Leukoc. Biol., 2008, Vol. 84, pp. 1492-1500.

75. Rahman M., Roller J., Zhang S., Syk I., Menger M.D., Jeppsson B., Thorlacius H. Metalloproteinases regulate CD40L shedding from platelets and pulmonary recruitment of neutrophils in abdominal sepsis. Inflamm. Res., 2012, Vol. 61, pp. 571-579.

76. Ramadan A. Ali, Leah M. Wuescher, Randall G. Worth. Platelets: essential components of the immune system. Curr. Trends Immunol., 2015, Vol. 16, pp. 65-78.

77. Rosenfeld S.I., Looney R.J., Leddy J.P., Phipps D.C., Abraham G.N., Anderson C.L. Human platelet Fc receptor for immunoglobulin G. Identification as a 40,000-molecular-weight membrane protein shared by monocytes. J. Clin. Invest., 1985, Vol. 76, no. 6, pp. 2317-2122.

78. Rossaint J., Herter J.M., van Aken H., Napirei M., Döring Y., Weber C. Soehnlein O., Zarbock A. Synchronized integrin engagement and chemokine activation is crucial in neutrophil extracellular trap-mediated sterile inflammation. Blood, 2014, Vol. 123, no. 16, pp. 2573-2584.

79. Rossaint J., Kühne K., Skupski J., van Aken H., Looney M.R., Hidalgo A., Zarbock A. Directed transport of neutrophil-derived extracellular vesicles enables platelet-mediated innate immune response. Nat. Commun., 2016, no. 7, 13464. doi: 10.1038/ncomms13464.

80. Rouhiainen A., Imai S., Rauvala H., Parkkinen J. Occurrence of amphoterin (HMG1) as an endogenous protein of human platelets that is exported to the cell surface upon platelet activation. Thromb. Haemost., 2000, Vol. 84, no. 6, pp. 1087-1094.

81. Rozman P., Bolta Z. Use of platelet growth factors in treating wounds and soft-tissue injuries.Acta Dermatovenerol. Alp. Panonica Adriat., 2007, Vol. 16, pp. 155-165.

82. Scheuerer B., Ernst M., Dürrbaum-Landmann I., Fleischer J., Grage-Griebenow E., Brandt E., Flad H.D., Petersen F. The CXC-chemokine platelet factor 4 promotes monocyte survival and induces monocyte differentiation into macrophages.Blood, 2000, Vol. 95, pp. 1158-1166.

83. Scull C.M., Hays W.D., Fischer T.H. Macrophage pro-inflammatory cytokine secretion is enhanced following interaction with autologous platelets. J. Inflamm. (Lond.), 2010, no. 7, pp. 53-58.

84. Shiraki R., Inoue N., Kawasaki S., Takei A., Kadotani M., Ohnishi U., Ejiri J., Kobayashi S., Hirata K., Kawashima S., Yokoyama M. Expression of Toll-like receptors on human platelets. Thromb. Res., 2004, Vol. 113, pp. 375-385.

85. Simon D.I., Chen Z., Xu H., Li C.Q., Dong J.F., McIntire L.V., Ballantyne C.M., Zhang L., Furman M.I., Berndt M.C., López J.A. Platelet glycoprotein ibalpha is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/ CD18). J. Exp. Med., 2000, Vol. 192, pp. 193-204.

86. Spycher M.O., Nydegger U.E. Participation of the blood platelet in immune reactions due to plateletcomplement interaction.Infusionsther. Transfusionsmed., 1995, Vol. 22, no. 1, pp. 36-43.

87. Steinhubl. S.R., Badimon J.J., Bhatt D.L., Herbert J.M., Luscher T.F. Clinical evidence for anti-inflammatory effects of anti-platelet therapy Steinhubl in patients with atherothrombotic disease. Vasc. Med., 2007, Vol. 12, no. 2, pp. 113-122.

88. Stephen J., Emerson B., Fox K.A., Dransfield I. The uncoupling of monocyte-platelet interactions from the induction of proinflammatory signaling in monocytes. J. Immunol., 2013, Vol. 191, no. 11, pp. 5677-5683.

89. Tilley S.L., Coffman T.M., Koller B.H. Mixed messages: modulation of inflammation and immune responses by prostaglandins and thromboxanes. J. Clin. Invest., 2001, Vol. 108, pp. 15-23.

90. Vieira-de-Abreu A., Campbell R.A., Weyrich A.S., Zimmerman G.A. Platelets: versatile effector cells in hemostasis, inflammation, and the immune continuum. Semin. Immunopathol., 2012, Vol. 3, no. 1, pp. 5-30.

91. Violi F., Pignatelli P. Platelet NOX a novel target for anti-thrombotic treatment. Thromb. Haemost., 2014, Vol. 111, no. 5, pp. 817-823.

92. Waehre T., Damas J.K., Pedersen T.M., Gullestad L., Yndestad A., Andreassen A.K., Froland S.S., Semb A.G., Hansteen V., Gjertsen E., Ueland T., Brosstad F., Solum N.O., Aukrust P. Clopidogrel increases expression of chemokines in peripheral blood mononuclear cells in patients with coronary artery disease: results of a doubleblind placebo-controlled study.J. Thromb. Haemost., 2006, Vol. 4, no. 10, pp. 2140-2147.

93. Weltermann A., Wolzt M., Petersmann K. Czerni C., Graselli U., Lechner K., Kyrle P.A. Large amounts of vascular endothelial growth factor at the site of hemostatic plug formation in vivo. Arterioscler. Thromb. Vasc. Biol., 1999, Vol. 19, pp. 1757-1760.

94. Xiang B., Zhang G., Guo L., Li X-A., Morris A.J., Daugherty A., Whiteheart S.W., Smyth S.S., Li Z. Platelets protect from septic shock by inhibiting macrophage-dependent inflammation via the cyclooxygenase 1 signalling pathway. Nat. Commun., 2013, no. 4, p. 2657.

95. Yeaman M.R. Platelets in defense against bacterial pathogens. Cell Mol. Life Sci., 2010, Vol. 67, no. 4, pp. 525-544.

96. Zamora C., Cantó E., Nieto J.C., Ortiz M.A., Diaz-Torné C., Diaz-Lopez C., Llobet J.M., Juarez C., Vidal S. Functional consequences of platelet binding to T lymphocytes in inflammation. J. Leukoc. Biol., 2013, Vol. 94, no. 3, pp. 521-529.

97. Zander D.M., Klinger M. The blood platelets contribution to innate host defense – what they have learned from their big brothers. Biotechnol. J., 2009, Vol. 4, no. 6, pp. 914-926.

98. Zarbock A., Polanowska-Grabowska R.K., Ley K. Platelet-neutrophil-interactions: linking hemostasis and inflammation. Blood Rev., 2007, Vol. 21, no. 2, pp. 99-111.

99. Zhu L., Huang Z., Stålesen R., Hansson G.K., Li N. Platelets provoke distinct dynamics of immune responses by differentially regulating CD4 + T-cell proliferation. J. Thromb. Haemost., 2014, Vol. 12, pp. 1156-1165.