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Inhibitory effects of lipoteichoic acid from Staphylococcus aureus on platelet function and platelet–monocyte aggregation

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Abstract

Objective

Lipoteichoic acid (LTA) from Staphylococcus aureus has been demonstrated to inhibit agonist-stimulated platelet aggregation. However, its effects on platelet inflammatory mediator release and platelet–monocyte aggregation are still unclear. In the present study, LTA is examined for its anti-inflammatory properties and effects on platelet–monocyte aggregation.

Methods

Blood samples were obtained from 5 healthy volunteers who had taken no medicine in the previous 2 weeks. Washed platelets were prepared and incubated with LTA (0.5–2.0 μg/mL), then platelet aggregation, P-selectin expression, and soluble CD40L (sCD40L) release were measured by light transmission aggregometry, flow cytometry and enzyme-linked immunoassays, respectively. Platelet–monocyte aggregate formation in whole blood was measured by flow cytometry. Thrombin was used as a stimulant.

Results

LTA dose-dependently decreased platelet aggregation from 89.32 ± 10.24% to 36.28 ± 9.01% (P < 0.05), sCD40L release from 3.28 ± 0.76 to 1.13 ± 0.45 ng/mL (P < 0.05) and surface P-selectin expression from 82.01 ± 11.20 to 22.78 ± 6.42% (P < 0.05). In human whole blood, 1.0 μg/mL LTA inhibited platelet–monocyte aggregation from 78.19 ± 10.94 to 38.24 + 8.74% (P < 0.05).

Conclusions

These results indicate that LTA from S. aureus can inhibit platelet-dependent inflammatory mediator release and platelet–monocyte aggregation. These findings suggest that LTA-mediated functional alteration of platelets may contribute to immune evasion of S. aureus.

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References

  1. Gordon RJ, Lowy FD. Pathogenesis of methicillin-resistant Staphylococcus aureus infection. Clin Infect Dis. 2008;46(Suppl 5):S350–9.

    Article  PubMed  CAS  Google Scholar 

  2. Foster TJ. Immune evasion by Staphylococci. Nat Rev Microbiol. 2005;3:948–58.

    Article  PubMed  CAS  Google Scholar 

  3. Peacock SJ, Moore CE, Justice A, Kantzanou M, Story L, Mackie K, et al. Virulent combinations of adhesion and toxin genes in natural populations of Staphylococcus aureus. Infect Immun. 2002;70:4987–96.

    Article  PubMed  CAS  Google Scholar 

  4. Wu B, Zhang W, Huang J, Liu H, Zhang T, et al. Effect of recombinant Panton-Valentine leukocidin in vitro on apoptosis and cytokine production of human alveolar macrophages. Can J Microbiol. 2010;56:229–35.

    Article  PubMed  CAS  Google Scholar 

  5. Prevost G, Cribier B, Couppie P, Petiau P, Supersac G, Monteil H, et al. Panton-Valentine leucocidin and γ-hemolysin from Staphylococcus aureus ATCC 49775 are encoded by distinct genetic loci and have different biological activities. Infect Immun. 1995;63:4121–9.

    PubMed  CAS  Google Scholar 

  6. De Kimpe SJ, Kengatharan M, Thiemermann C, Vane JR. The cell wall components peptidoglycan and lipoteichoic acid from Staphylococcus aureus act in synergy to cause shock and multiple organ failure. Proc Natl Acad Sci USA. 1995;92:10359–63.

    Article  PubMed  Google Scholar 

  7. Kengatharan KM, De Kimpe S, Robson C, Foster SJ, Thiemermann C. Mechanism of gram-positive shock: identification of peptidoglycan and lipoteichoic acid moieties essential in the induction of nitric oxide synthase, shock, and multiple organ failure. J Exp Med. 1998;188:305–15.

    Article  PubMed  CAS  Google Scholar 

  8. Bhakdi S, Klonisch T, Nuber P, Fischer W. Stimulation of monokine production by lipoteichoic acids. Infect Immun. 1991;59:4614–20.

    PubMed  CAS  Google Scholar 

  9. Han SH, Kim JH, Martin M, Michalek SM, Nahm MH. Pneumococcal lipoteichoic acid (LTA) is not as potent as staphylococcal LTA in stimulating Toll-like receptor 2. Infect Immun. 2003;71:5541–8.

    Article  PubMed  CAS  Google Scholar 

  10. Klinger MH, Jelkmann W. Role of blood platelets in infection and inflammation. J Interferon Cytokine Res. 2002;22:913–22.

    Article  PubMed  CAS  Google Scholar 

  11. Sheu JR, Lee CR, Lin CH, Hsiao G, Ko WC, Chen YC, et al. Mechanisms involved in the antiplatelet activity of Staphylococcus aureus lipoteichoic acid in human platelets. J Thromb Haemost. 2000;83:777–84.

    CAS  Google Scholar 

  12. Hermann A, Rauch BH, Braun M, Weber A, Schrör K. Platelet CD40 ligand (CD40L)—subcellular localization, regulation of expression, and inhibition by clopidogrel. Platelets. 2001;12:74–82.

    Article  PubMed  CAS  Google Scholar 

  13. Murohara T, Parkinson SJ, Waldman SA, Lefer AM. Inhibition of nitric oxide biosynthesis promotes P-selectin expression in platelets. Role of protein kinase C. Arterioscler Thromb Vasc Biol. 1995;15:2068–75.

    Article  PubMed  CAS  Google Scholar 

  14. Delvaeye M, Conway EM. Coagulation and innate immune responses: can we view them separately? Blood. 2009;114:2367–74.

    Article  PubMed  CAS  Google Scholar 

  15. Ellingsen E, Morath S, Flo T, Schromm A, Hartung T, Thiemermann C, et al. Induction of cytokine production in human T cells and monocytes by highly purified lipoteichoic acid: involvement of Toll-like receptors and CD14. Med Sci Monit. 2002;8:149–56.

    Google Scholar 

  16. Hashimoto M, Imamur Y, Yasuoka J, Kotani S, Kusumoto S, Susa Y, et al. A novel cytokine-inducing glycolipid isolated from lipoteichoic acid fraction of Enterococcus hirae ATCC 9790: a fundamental structure of the hydrophilic part. Glycoconj J. 1999;16:213–21.

    Article  PubMed  CAS  Google Scholar 

  17. Lehner MD, Morath S, Michelsen KS, Schumann RR, Hartung T. Induction of cross-tolerance by lipopolysaccharide and highly purified lipoteichoic acid via different Toll-like receptors independent of paracrine mediators. J Immunol. 2001;166:5161–7.

    PubMed  CAS  Google Scholar 

  18. Blease K, Chen Y, Hellewell PG, Anne BG. Lipoteichoic acid inhibits lipopolysaccharide-induced adhesion molecule expression and IL-8 release in human lung microvascular endothelial Cells. J Immunol. 1999;163:6139–47.

    PubMed  CAS  Google Scholar 

  19. Li Z, Xi X, Gu M, Feil R, Ye RD, Du XP, et al. A stimulatory role for cGMP-dependent protein kinase in platelet activation. Cell. 2003;112:77–86.

    Article  PubMed  CAS  Google Scholar 

  20. Beachey EH, Chiang TM, Ofek I, Kang AH. Interaction of lipoteichoic acid of group A. Streptococci with human platelets. Infect Immun. 1977;16:649–54.

    PubMed  CAS  Google Scholar 

  21. Moshfegh K, Redondo M, Julmy F, Wuillemin WA, Gebauer MU, Meyer BJ, et al. Antiplatelet effects of clopidogrel compared with aspirin after myocardial infarction: enhanced inhibitory effects of combination therapy. J Am Coll Cardiol. 2000;36:699–705.

    Article  PubMed  CAS  Google Scholar 

  22. Henn V, Slupsky JR, Anagnostopoulos I, Kroczek RA, Förster R, Gräfe M, et al. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature. 1998;391:591–4.

    Article  PubMed  CAS  Google Scholar 

  23. Weyrich AS, Zimmerman GA. Platelets: signaling cells in the immune continuum. Trends Immunol. 2004;25:489–95.

    Article  PubMed  CAS  Google Scholar 

  24. Yeaman MR. Platelets in defense against bacterial pathogens. Cell Mol Life Sci. 2010;67:525–44.

    Article  PubMed  CAS  Google Scholar 

  25. Tang YQ, Yeaman MR, Selsted ME. Antimicrobial peptides from human platelets. Infect Immun. 2002;70:6524–33.

    Article  PubMed  CAS  Google Scholar 

  26. Weyrich AS, Lindemann S, Zimmerman GA. The evolving role of platelets in inflammation. J Thromb Haemost. 2003;1:1897–905.

    Article  PubMed  CAS  Google Scholar 

  27. Gursel O, Atay AA, Kurekci E, Avcu F, Nevruz O, Senses Z, et al. Platelet aggregation in children with Helicobacter pylori infection. Clin Appl Thromb Hemost. 2010;16:637–42.

    Google Scholar 

  28. Escolar G, White JG. Changes in glycoprotein expression after platelet activation: differences between in vitro and in vivo studies. Thromb Haemost. 2000;83:371–86.

    PubMed  CAS  Google Scholar 

  29. Gawaz M, Langer H, May AE. Platelets in inflammation and atherogenesis. J Clin Invest. 2005;115:3378–84.

    Article  PubMed  CAS  Google Scholar 

  30. Fagerstam JP, Whiss PA, Strom M, Andersson RG. Expression of platelet P-selectin and detection of soluble P-selectin, NPY and RANTES in patients with inflammatory bowel disease. Inflamm Res. 2000;49:466–72.

    Article  PubMed  CAS  Google Scholar 

  31. Dole VS, Bergmeier W, Patten IS, Hirahashi J, Mayadas TN, Wagner DD, et al. PSGL-1 regulates platelet P-selectin-mediated endothelial activation and shedding of P-selectin from activated platelets. Thromb Haemost. 2007;98:806–12.

    PubMed  CAS  Google Scholar 

  32. Mayadas TN, Johnson RC, Rayburn H, Hynes RO, Wagner DD. Leukocyte rolling and extravasation are severely compromised in P selectin-deficient mice. Cell. 1993;74:541–54.

    Article  PubMed  CAS  Google Scholar 

  33. Lederman S, Yellin MJ, Inghirami G, Lee JJ, Knowles DM, Chess L. Molecular interactions mediating T-B lymphocyte collaboration in human lymphoid follicles. Roles of T cell-B-cell-activating molecule (5c8 antigen) and CD40 in contact-dependent help. J Immunol. 1992;149:3817–26.

    PubMed  CAS  Google Scholar 

  34. Freedman JE. CD40–CD40L and platelet function: beyond hemostasis. Circ Res. 2003;92:944–6.

    Article  PubMed  CAS  Google Scholar 

  35. Stout RD, Suttles J. The many roles of CD40 in cell mediated inflammatory responses. Immunol Today. 1996;17:487–92.

    Article  PubMed  CAS  Google Scholar 

  36. Nathan C. Points of control in inflammation. Nature. 2002;420:846–52.

    Article  PubMed  CAS  Google Scholar 

  37. Vanichakarn P, Blair P, Wu C, Freedman JE, Chakrabarti S. Neutrophil CD40 enhances platelet-mediated inflammation. Thromb Res. 2008;122:346–58.

    Article  PubMed  CAS  Google Scholar 

  38. McIntyre TM, Prescott SM, Weyrich AS, Zimmerman GA. Cell–cell interactions: leukocyte–endothelial interactions. Curr Opin Hematol. 2003;10:150–8.

    Article  PubMed  CAS  Google Scholar 

  39. Russo S, Bussolati B, Deambrosis I, Mariano F, Camussi G. Platelet-activating factor mediates CD40-dependent angiogenesis and endothelial-smooth muscle cell interaction. J Immunol. 2003;171:5489–97.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (Number: 30670918) and the Science and Technology Project of Guangdong Province (Number: 0911220600105).

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Correspondence to Ben-Quan Wu.

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Responsible editor: Makoto Katori.

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Wu, BQ., Zhi, MJ., Liu, H. et al. Inhibitory effects of lipoteichoic acid from Staphylococcus aureus on platelet function and platelet–monocyte aggregation. Inflamm. Res. 60, 775–782 (2011). https://doi.org/10.1007/s00011-011-0333-6

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  • DOI: https://doi.org/10.1007/s00011-011-0333-6

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