Platelets modulate multiple markers of neutrophil function in response to in vitro Toll-like receptor stimulation


Autoři: Kathryn E. Hally aff001;  Georgina K. Bird aff002;  Anne C. La Flamme aff002;  Scott A. Harding aff002;  Peter D. Larsen aff001
Působiště autorů: Department of Surgery and Anaesthesia, University of Otago, Wellington, New Zealand aff001;  School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand aff002;  Wellington Cardiovascular Research Group, Wellington, New Zealand aff003;  Department of Cardiology, Wellington Hospital, Wellington, New Zealand aff004
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223444

Souhrn

Introduction

In addition to their role in facilitating leukocyte-mediated inflammation, platelets can dampen leukocyte pro-inflammatory responses in some contexts. Consequently, platelets are increasingly appreciated as regulators of inflammation. Together, platelets and neutrophils play a role in inflammation through Toll-like receptor (TLR) expression, although we do not fully understand how platelets shape neutrophil responses to TLR stimulation. Here, we aimed to determine the extent to which platelets can modulate neutrophil function in response to in vitro stimulation with TLR4, TLR2/1, and TLR2/6 agonists.

Methods

Neutrophils from 10 healthy individuals were cultured alone or with autologous platelets. Neutrophils ± platelets were left unstimulated or were stimulated with 1 or 100 ng/mL lipopolysaccharide (LPS; a TLR4 agonist), Pam3CSK4 (a TLR2/1 agonist) and fibroblast-stimulating lipopeptide (FSL)-1 (a TLR2/6 agonist). Neutrophil activation and phagocytic activity were assessed by flow cytometry, and elastase and interleukin-8 secretion were assessed by ELISA.

Results

The addition of platelets attenuated neutrophil CD66b and CD11b expression in response to various doses of Pam3CSK4 and FSL-1. Furthermore, platelet co-culture was associated with higher CD62L expression (indicating reduced CD62L shedding) in response to these TLR agonists. Platelets also reduced elastase secretion in unstimulated cultures and in response to low-dose TLR stimulation. Conversely, platelet co-culture increased neutrophil phagocytosis in unstimulated cultures and in response to low-dose Pam3CSK4 and FSL-1. Platelets also increased IL-8 secretion in response to low-dose LPS.

Conclusion

Platelets are complex immunomodulators that can attenuate some, and simultaneously augment other, neutrophil functions. This modulation can occur both in the absence and presence of TLR stimulation.

Klíčová slova:

Inflammation – Inflammatory diseases – Neutrophils – Phagocytosis – Platelet activation – Platelets – Secretion – Toll-like receptors


Zdroje

1. Yeaman MR. Platelets: at the nexus of antimicrobial defence. Nature Reviews Microbiology. 2014; 12: 426–37. doi: 10.1038/nrmicro3269 24830471

2. Clark SR, Ma AC, Tavener SA, McDonald B, Goodarzi Z, Kelly MM, et al. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med. 2007; 13: 463–9. doi: 10.1038/nm1565 17384648

3. Verschoor A, Neuenhahn M, Navarini AA, Graef P, Plaumann A, Seidlmeier A, et al. A platelet-mediated system for shuttling blood-borne bacteria to CD8[alpha]+ dendritic cells depends on glycoprotein GPIb and complement C3. Nat Immunol. 2011; 12: 1194–201. doi: 10.1038/ni.2140 22037602

4. 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; 83: 196–8. doi: 10.1111/j.1440-1711.2005.01314.x 15748217

5. Shiraki R, Inoue N, Kawasaki S, Takei A, Kadotani M, Ohnishi Y, et al. Expression of Toll-like receptors on human platelets. Thromb Res. 2004; 113: 379–85. doi: 10.1016/j.thromres.2004.03.023 15226092

6. Hally KE, La Flamme AC, Larsen PD, Harding SA. Platelet Toll-like receptor (TLR) expression and TLR-mediated platelet activation in acute myocardial infarction. Thromb Res. 2017; 158: 8–15. doi: 10.1016/j.thromres.2017.07.031 28783513

7. Blair P, Rex S, Vitseva O, Beaulieu L, Tanriverdi K, Chakrabarti S, 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: 346–54. doi: 10.1161/CIRCRESAHA.108.185785 19106411

8. Rivadeneyra L, Carestia A, Etulain J, Pozner RG, Fondevila C, Negrotto S, 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: 235–43. doi: 10.1016/j.thromres.2013.11.028 24331207

9. Zhang G, Han J, Welch EJ, Ye RD, Voyno-Yasenetskaya TA, Malik AB, 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. doi: 10.4049/jimmunol.0802884 19494325

10. Hally KE, La Flamme AC, Harding SA, Larsen PD. The effects of aspirin and ticagrelor on Toll-like receptor (TLR)-mediated platelet activation: results of a randomized, cross-over trial. Platelets. 2018: 1–9.

11. Stocker TJ, Ishikawa-Ankerhold H, Massberg S, Schulz C. Small but mighty: Platelets as central effectors of host defense. Thromb Haemost. 2017; 117: 651–61. doi: 10.1160/TH16-12-0921 28203681

12. Ståhl A-l, Svensson M, Mörgelin M, Svanborg C, Tarr PI, Mooney JC, et al. Lipopolysaccharide from enterohemorrhagic Escherichia coli binds to platelets through TLR4 and CD62 and is detected on circulating platelets in patients with hemolytic uremic syndrome. Blood. 2006; 108: 167–76. doi: 10.1182/blood-2005-08-3219 16514062

13. Linke B, Schreiber Y, Picard-Willems B, Slattery P, Nusing RM, Harder S, et al. Activated Platelets Induce an Anti-Inflammatory Response of Monocytes/Macrophages through Cross-Regulation of PGE2 and Cytokines. Mediators Inflamm. 2017; 2017: 1463216. doi: 10.1155/2017/1463216 28592915

14. Jancinova V, Drabikova K, Petrikova M, Nosal R. Blood platelets decrease concentration of reactive oxygen species produced by polymorphonuclear leukocytes. Bratisl Lek Listy. 2004; 105: 250–5. 15543845

15. Reinisch CM, Dunzendorfer S, Pechlaner C, Ricevuti G, Wiedermann CJ. The inhibition of oxygen radical release from human neutrophils by resting platelets is reversed by administration of acetylsalicylic acid or clopidogrel. Free Radic Res. 2001; 34: 461–6. doi: 10.1080/10715760100300401 11378529

16. Hally KE, La Flamme AC, Harding SA, Larsen PD. Platelets regulate leucocyte responses to Toll-like receptor stimulation. Clinical & Translational Immunology. 2018; 7: e1036.

17. Ziegler M, Wang X, Peter K. Platelets in cardiac ischaemia/reperfusion injury: a promising therapeutic target. Cardiovasc Res. 2019; 115: 1178–88. doi: 10.1093/cvr/cvz070 30906948

18. Xiang B, Zhang G, Guo L, Li XA, Morris AJ, Daugherty A, et al. Platelets protect from septic shock by inhibiting macrophage-dependent inflammation via the cyclooxygenase 1 signalling pathway. Nature Communications. 2013; 4: 2657. doi: 10.1038/ncomms3657 24150174

19. Bain W, Olonisakin T, Yu M, Qu Y, Hulver M, Xiong Z, et al. Platelets inhibit apoptotic lung epithelial cell death and protect mice against infection-induced lung injury. Blood Advances. 2019; 3: 432–45. doi: 10.1182/bloodadvances.2018026286 30733303

20. Walsh TG, Poole AW. Do platelets promote cardiac recovery after myocardial infarction: roles beyond occlusive ischemic damage. Am J Physiol Heart Circ Physiol. 2018; 314: H1043–h8. doi: 10.1152/ajpheart.00134.2018 29547023

21. Gros A, Ollivier V, Ho-Tin-Noe B. Platelets in inflammation: regulation of leukocyte activities and vascular repair. Front Immunol. 2014; 5: 678. doi: 10.3389/fimmu.2014.00678 25610439

22. Assinger A, Laky M, Badrnya S, Esfandeyari A, Volf I. Periodontopathogens induce expression of CD40L on human platelets via TLR2 and TLR4. Thromb Res. 2012; 130: e73–e8. doi: 10.1016/j.thromres.2012.04.017 22608210

23. Zarbock A, Singbartl K, Ley K. Complete reversal of acid-induced acute lung injury by blocking of platelet-neutrophil aggregation. J Clin Invest. 2006; 116: 3211–9. doi: 10.1172/JCI29499 17143330

24. McDonald B, Davis RP, Kim SJ, Tse M, Esmon CT, Kolaczkowska E, et al. Platelets and neutrophil extracellular traps collaborate to promote intravascular coagulation during sepsis in mice. Blood. 2017; 129: 1357–67. doi: 10.1182/blood-2016-09-741298 28073784

25. Herbertsson H, Bengtsson T. Role of platelets and the arachidonic acid pathway in the regulation of neutrophil oxidase activity. Scand J Clin Lab Invest. 2001; 61: 641–9. doi: 10.1080/003655101753268008 11768324

26. Losche W, Dressel M, Krause S, Redlich H, Spangenberg P, Heptinstall S. Contact-induced modulation of neutrophil elastase secretion and phagocytic activity by platelets. Blood Coagul Fibrinolysis. 1996; 7: 210–3. doi: 10.1097/00001721-199603000-00025 8735821

27. Del Principe D, Menichelli A, Di Giulio S, De Matteis W, Giordani M, Pentassuglio AM, et al. Stimulated platelets release factor(s) affecting the in vitro response of human polymorphonuclear cells. J Leukoc Biol. 1990; 48: 7–14. doi: 10.1002/jlb.48.1.7 2113564

28. Fortunati E, Kazemier KM, Grutters JC, Koenderman L, Van den Bosch vJMM. Human neutrophils switch to an activated phenotype after homing to the lung irrespective of inflammatory disease. Clin Exp Immunol. 2009; 155: 559–66. doi: 10.1111/j.1365-2249.2008.03791.x 19077082

29. van Oostrom AJ, van Wijk JP, Sijmonsma TP, Rabelink TJ, Castro Cabezas M. Increased expression of activation markers on monocytes and neutrophils in type 2 diabetes. The Netherlands Journal of Medicine. 2004; 62: 320–5. 15635816

30. Stokes KY, Granger DN. Platelets: a critical link between inflammation and microvascular dysfunction. The Journal of Physiology. 2012; 590: 1023–34. doi: 10.1113/jphysiol.2011.225417 22183721

31. Gudbrandsdottir S, Hasselbalch HC, Nielsen CH. Activated platelets enhance IL-10 secretion and reduce TNF-alpha secretion by monocytes. J Immunol. 2013; 191: 4059–67. doi: 10.4049/jimmunol.1201103 24048901

32. Nami N, Feci L, Napoliello L, Giordano A, Lorenzini S, Galeazzi M, et al. Crosstalk between platelets and PBMC: New evidence in wound healing. Platelets. 2016; 27: 143–8. doi: 10.3109/09537104.2015.1048216 26030799

33. Sadallah S, Eken C, Martin PJ, Schifferli JA. Microparticles (ectosomes) shed by stored human platelets downregulate macrophages and modify the development of dendritic cells. J Immunol. 2011; 186: 6543–52. doi: 10.4049/jimmunol.1002788 21525379

34. Jancinova V, Drabikova K, Nosal R, Petrikova M, Ciz M, Lojek A, et al. Inhibition of FMLP-stimulated neutrophil chemiluminescence by blood platelets increased in the presence of the serotonin-liberating drug chloroquine. Thromb Res. 2003; 109: 293–8. doi: 10.1016/s0049-3848(03)00239-1 12818253

35. Deree J, Lall R, Melbostad H, Grant M, Hoyt DB, Coimbra R. Neutrophil degranulation and the effects of phosphodiesterase inhibition. J Surg Res. 2006; 133: 22–8. doi: 10.1016/j.jss.2006.02.031 16690368

36. Lacy P. Mechanisms of Degranulation in Neutrophils. Allergy, Asthma, and Clinical Immunology: Official Journal of the Canadian Society of Allergy and Clinical Immunology. 2006; 2: 98–108.

37. Le Cabec V, Carreno S, Moisand A, Bordier C, Maridonneau-Parini I. Complement receptor 3 (CD11b/CD18) mediates type I and type II phagocytosis during nonopsonic and opsonic phagocytosis, respectively. J Immunol. 2002; 169: 2003–9. doi: 10.4049/jimmunol.169.4.2003 12165526

38. Diacovo TG, Roth SJ, Buccola JM, Bainton DF, Springer TA. Neutrophil rolling, arrest, and transmigration across activated, surface-adherent platelets via sequential action of P-selectin and the beta 2-integrin CD11b/CD18. Blood. 1996; 88: 146–57. 8704169

39. Corken A, Russell S, Dent J, Post SR, Ware J. Platelet glycoprotein Ib-IX as a regulator of systemic inflammation. Arterioscler Thromb Vasc Biol. 2014; 34: 996–1001. doi: 10.1161/ATVBAHA.113.303113 24504734

40. Klarstrom Engstrom K, Brommesson C, Kalvegren H, Bengtsson T. Toll like receptor 2/1 mediated platelet adhesion and activation on bacterial mimetic surfaces is dependent on src/Syk-signaling and purinergic receptor P2X1 and P2Y12 activation. Biointerphases. 2014; 9: 041003. doi: 10.1116/1.4901135 25553878

41. Falker K, Klarstrom-Engstrom K, Bengtsson T, Lindahl TL, Grenegard M. 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: 279–86. doi: 10.1016/j.cellsig.2013.11.011 24240055

42. Senis YA, Mazharian A, Mori J. Src family kinases: at the forefront of platelet activation. Blood. 2014; 124: 2013–24. doi: 10.1182/blood-2014-01-453134 25115887

43. Assinger A, Laky M, Schabbauer G, Hirschl AM, Buchberger E, Binder BR, et al. Efficient phagocytosis of periodontopathogens by neutrophils requires plasma factors, platelets and TLR2. J Thromb Haemost. 2011; 9: 799–809. doi: 10.1111/j.1538-7836.2011.04193.x 21251195

44. Belaaouaj A, Kim KS, Shapiro SD. Degradation of outer membrane protein A in Escherichia coli killing by neutrophil elastase. Science. 2000; 289: 1185–8. doi: 10.1126/science.289.5482.1185 10947984

45. Kawabata K, Hagio T, Matsuoka S. The role of neutrophil elastase in acute lung injury. Eur J Pharmacol. 2002; 451: 1–10. doi: 10.1016/s0014-2999(02)02182-9 12223222

46. Doring G. The role of neutrophil elastase in chronic inflammation. Am J Respir Crit Care Med. 1994; 150: S114–7. doi: 10.1164/ajrccm/150.6_Pt_2.S114 7952645

47. Hammond ME, Lapointe GR, Feucht PH, Hilt S, Gallegos CA, Gordon CA, et al. IL-8 induces neutrophil chemotaxis predominantly via type I IL-8 receptors. J Immunol. 1995; 155: 1428–33. 7636208

48. Sahoo M, del Barrio L, Miller MA, Re F. Neutrophil Elastase Causes Tissue Damage That Decreases Host Tolerance to Lung Infection with Burkholderia Species. PLoS Pathog. 2014; 10: e1004327. doi: 10.1371/journal.ppat.1004327 25166912

49. Bardoel Bart W, Kenny Elaine F, Sollberger G, Zychlinsky A. The Balancing Act of Neutrophils. Cell Host Microbe. 2014; 15: 526–36. doi: 10.1016/j.chom.2014.04.011 24832448

50. Middleton EA, Rondina MT, Schwertz H, Zimmerman GA. Amicus or Adversary Revisited: Platelets in Acute Lung Injury and Acute Respiratory Distress Syndrome. Am J Respir Cell Mol Biol. 2018; 59: 18–35. doi: 10.1165/rcmb.2017-0420TR 29553813

51. Lee KH, Hui KP, Tan WC. Thrombocytopenia in sepsis: a predictor of mortality in the intensive care unit. Singapore Med J. 1993; 34: 245–6. 8266183

52. Wuescher LM, Takashima A, Worth RG. A novel conditional platelet depletion mouse model reveals the importance of platelets in protection against Staphylococcus aureus bacteremia. J Thromb Haemost. 2015; 13: 303–13. doi: 10.1111/jth.12795 25418277

53. de Stoppelaar SF, van 't Veer C, Claushuis TA, Albersen BJ, Roelofs JJ, van der Poll T. Thrombocytopenia impairs host defense in gram-negative pneumonia-derived sepsis in mice. Blood. 2014; 124: 3781–90. doi: 10.1182/blood-2014-05-573915 25301709

54. Hechler B, Zimmermann C, Rabouel Y, Magnenat S, Burban M, Boisramé-Helms J, et al. A Potential Protective Role of Platelets during Septic Shock Does Not Depend on Their Purinergic Receptors. Blood. 2016; 128: 2537–.

55. Martinod K, Wagner DD. Thrombosis: tangled up in NETs. Blood. 2014; 123: 2768–76. doi: 10.1182/blood-2013-10-463646 24366358

56. Schauer C, Janko C, Munoz LE, Zhao Y, Kienhofer D, Frey B, et al. Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines. Nat Med. 2014; 20: 511–7. doi: 10.1038/nm.3547 24784231

57. Looney MR, Nguyen JX, Hu Y, Van Ziffle JA, Lowell CA, Matthay MA. Platelet depletion and aspirin treatment protect mice in a two-event model of transfusion-related acute lung injury. The Journal of Clinical Investigation. 2009; 119: 3450–61. doi: 10.1172/JCI38432 19809160

58. Luo S, Wang Y, An Q, Chen H, Zhao J, Zhang J, et al. Platelets protect lung from injury induced by systemic inflammatory response. Sci Rep. 2017; 7: 42080. doi: 10.1038/srep42080 28155889

59. Abdulnour RE, Dalli J, Colby JK, Krishnamoorthy N, Timmons JY, Tan SH, et al. Maresin 1 biosynthesis during platelet-neutrophil interactions is organ-protective. Proc Natl Acad Sci U S A. 2014; 111: 16526–31. doi: 10.1073/pnas.1407123111 25369934

60. Frangogiannis NG. The inflammatory response in myocardial injury, repair, and remodelling. Nat Rev Cardiol. 2014; 11: 255–65. doi: 10.1038/nrcardio.2014.28 24663091

61. Lefer AM, Campbell B, Scalia R, Lefer DJ. Synergism Between Platelets and Neutrophils in Provoking Cardiac Dysfunction After Ischemia and Reperfusion. Role of Selectins. 1998; 98: 1322–8.

62. Hargrave B, Li F. Nanosecond pulse electric field activation of platelet-rich plasma reduces myocardial infarct size and improves left ventricular mechanical function in the rabbit heart. The journal of extra-corporeal technology. 2012; 44: 198–204. 23441560

63. Milioli M, Ibanez-Vea M, Sidoli S, Palmisano G, Careri M, Larsen MR. Quantitative proteomics analysis of platelet-derived microparticles reveals distinct protein signatures when stimulated by different physiological agonists. J Proteomics. 2015; 121: 56–66. doi: 10.1016/j.jprot.2015.03.013 25835965

64. Vélez P, Izquierdo I, Rosa I, García Á. A 2D-DIGE-based proteomic analysis reveals differences in the platelet releasate composition when comparing thrombin and collagen stimulations. Sci Rep. 2015; 5: 8198. doi: 10.1038/srep08198 25645904

65. Chatterjee M, Huang Z, Zhang W, Jiang L, Hultenby K, Zhu L, et al. Distinct platelet packaging, release, and surface expression of proangiogenic and antiangiogenic factors on different platelet stimuli. Blood. 2011; 117: 3907–11. doi: 10.1182/blood-2010-12-327007 21330475

66. Pokrovskaya ID, Aronova MA, Kamykowski JA, Prince AA, Hoyne JD, Calco GN, et al. STEM tomography reveals that the canalicular system and alpha-granules remain separate compartments during early secretion stages in blood platelets. J Thromb Haemost. 2016; 14: 572–84. doi: 10.1111/jth.13225 26663480


Článek vyšel v časopise

PLOS One


2019 Číslo 10

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

Léčba bolesti v ordinaci praktického lékaře
nový kurz
Autoři: MUDr. PhDr. Zdeňka Nováková, Ph.D.

Revmatoidní artritida: včas a k cíli
Autoři: MUDr. Heřman Mann

Jistoty a nástrahy antikoagulační léčby aneb kardiolog - neurolog - farmakolog - nefrolog - právník diskutují
Autoři: doc. MUDr. Štěpán Havránek, Ph.D., prof. MUDr. Roman Herzig, Ph.D., doc. MUDr. Karel Urbánek, Ph.D., prim. MUDr. Jan Vachek, MUDr. et Mgr. Jolana Těšínová, Ph.D.

Léčba akutní pooperační bolesti
Autoři: doc. MUDr. Jiří Málek, CSc.

Nové antipsychotikum kariprazin v léčbě schizofrenie
Autoři: prof. MUDr. Cyril Höschl, DrSc., FRCPsych.

Všechny kurzy
Kurzy Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se