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Biophysics

, Volume 63, Issue 3, pp 357–364 | Cite as

Modeling of Granule Secretion upon Platelet Activation through the TLR4-Receptor

  • A. S. Maiorov
  • T. O. Shepelyuk
  • F. A. Balabin
  • A. A. Martyanov
  • D. Y. NechipurenkoEmail author
  • A. N. Sveshnikova
Cell Biophysics
  • 9 Downloads

Abstract

This paper presents the mathematical modeling of the possibility of blood platelets activation by lipopolysaccharides, which are components of the cell wall of gram-negative bacteria, through the toll-like receptor TLR4. We have developed both complete and reduced models of the platelet signaling cascade triggered by TLR4 considering the known kinetics of intracellular signaling enzymes and the contents of the proteins that participate in the TLR4 signaling cascade in human platelets. The results of our simulation show that the concentration of the soluble CD14 protein, which is necessary for the activation of platelets by lipopolysaccharides via TLR4, is insufficient for platelet activation in the blood of healthy donors. Thus, our results suggest that blood platelets can be activated by lipopolysaccharides through TLR4 only in cases of strong activation of the immune system accompanied by an increase in CD14 concentration in the blood.

Keywords

intracellular signaling lipopolysaccharides Escherichia coli blood coagulation 

Abbreviation

LPS

lipopolysaccharide(s)

TLR

toll-like receptor

LBP

LPS-binding protein (the plasma protein that binds LPS and delivers it to the CD14 protein)

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References

  1. 1.
    A. D. Michelson, Platelets (Elsevier, 2013).Google Scholar
  2. 2.
    G. Zhang, J. Han, E. J. Welchet, et al., J. Immunol. 182 (12), 7997 (2009).CrossRefGoogle Scholar
  3. 3.
    G. Andonegui, S. M. Kerfoot, K. McNagny, et al., Blood 106 (7), 2417 (2005).CrossRefGoogle Scholar
  4. 4.
    V. Matus, J. G. Valenzuela, P. Hidalgo, et al., PLoS One 4, 1 (2017).Google Scholar
  5. 5.
    A. L. Ståhl, M. Svensson, M. Mörgelin, et al., Blood 108 (1), 167 (2006).CrossRefGoogle Scholar
  6. 6.
    N. E. Gomes, M. K. C. Brunialti, M. E. Mendes, et al., Braz. J. Med. Biol. Res. 43, 853 (2010).CrossRefGoogle Scholar
  7. 7.
    S. Akira and K. Takeda, Nat. Rev. Immunol. 4, 499 (2004).CrossRefGoogle Scholar
  8. 8.
    G. Andonegui, S. M. Kerfoot, K. McNagny, et al., Blood 106, 2417 (2005).CrossRefGoogle Scholar
  9. 9.
    E. Ampofo, I. Müller, I. N. Dahmke, et al., Thromb. Res. 136, 996 (2015).CrossRefGoogle Scholar
  10. 10.
    R. Aslam, E. R. Speck, M. Kim, et al., Blood 107, 637 (2006). doi 10.1182/blood-2005-06-2202CrossRefGoogle Scholar
  11. 11.
    G. C. Sharp, H. Ma, P. T. K. Saunders, and J. E. Norman, PLoS One 8 (7), e70180 (2013).Google Scholar
  12. 12.
    F. Rendu and B. Brohard-Bohn, Platelets 12, 261 (2001).CrossRefGoogle Scholar
  13. 13.
    M. H. Fukami, J. S. Bauer, G. J. Stewart, and L. Salganicoff, J. Cell Biol. 77, 389 (1978).CrossRefGoogle Scholar
  14. 14.
    S. Vogel, R. Bodenstein, Q. Chen, et al., J. Clin. Invest. 125 (12), 4638 (2015).CrossRefGoogle Scholar
  15. 15.
    X. Yang, H. Wang, M. Zhang, et al., Diagn. Pathol. 10, 134 (2015).CrossRefGoogle Scholar
  16. 16.
    L. Petzold and A. Hindmarsh, LSODA: Livermore Solver of Ordinary Differential Equations (Lawrence Livermore National Laboratory, Livermore, CA, 1997).Google Scholar
  17. 17.
    A. C. Hindmarsh, ACM Signum Newsl. 15, 10 (1980).CrossRefGoogle Scholar
  18. 18.
    P. Mendes, S. Hoops, S. Sahle, et al., Methods Mol. Biol. 500, 17 (2009).CrossRefGoogle Scholar
  19. 19.
    D. B. Fogel, L. J. Fogel, W. Atmar, and G. B. Fogel, in Proceedings of tha First Annual Conference on Evolutionary Programming (1992), p. 175.zbMATHGoogle Scholar
  20. 20.
    J. Berthet, P. Damien, H. Hamzeh-Cognasse, et al., Br. J. Haematol. 151 (1), 89 (2010).CrossRefGoogle Scholar
  21. 21.
    B. S. Park, D. H. Song, H. M. Kim, et al., Nature 458, 1191 (2009).ADSCrossRefGoogle Scholar
  22. 22.
    H. J. Shin, H. Lee, J. D. Park, et al., Mol. Cells 24 (1), 119 (2007).Google Scholar
  23. 23.
    L. A. Ryan, J. Zheng, M. Brester, et al., J. Infect. Dis. 184 (6), 699 (2017).CrossRefGoogle Scholar
  24. 24.
    E. Hailman, T. Vasselon, M. Kelley, et al., J. Immunol. 156, 4384 (1996).Google Scholar
  25. 25.
    T. Kusunoki, S. D. Wright, Y. Inoue, and T. Miyanomae, Allergol. Int. 47, 271 (1998).CrossRefGoogle Scholar
  26. 26.
    P. G. Motshwene, M. C. Moncrieffe, J. G. Grossmann, et al., J. Biol. Chem. 284, 25404 (2009).CrossRefGoogle Scholar
  27. 27.
    S.-C. Lin, Y.-C. Lo, and H. Wu, Nature 465, 885 (2010).ADSCrossRefGoogle Scholar
  28. 28.
    H. Wu and J. R. Arron, BioEssays 25, 109605 (2003).CrossRefGoogle Scholar
  29. 29.
    C. W. Philipson, J. Bassaganya-Riera, M. Viladomiu, et al., PLoS One 10, e0137839 (2015).Google Scholar
  30. 30.
    L. Deng, Ch. Wang, E. Spencer, et al., Cell 103, 351 (2000).CrossRefGoogle Scholar
  31. 31.
    J. Napetschnig and H. Wu, Annu. Rev. Biophys. 42, 443 (2013).CrossRefGoogle Scholar
  32. 32.
    Z. A. Karim, J. Zhang, M. Banerjee, et al., Blood 121 (22), 4567 (2016).CrossRefGoogle Scholar
  33. 33.
    R. D. Moriarty, A. Cox, M. McCall, et al., J. Thromb. Haemost. 14, 797 (2016).CrossRefGoogle Scholar
  34. 34.
    C. N. Watson, S. W. Kerrigan, D. Cox, et al., Platelets 7104, 1 (2016).Google Scholar
  35. 35.
    J. M. Burkhart, M. Vaudel, S. Gambaryan, et al., Blood 120, e73 (2012).Google Scholar
  36. 36.
    J. Pugin, C. C. Schürer-Maly, D. Leturcq, et al., Proc. Natl. Acad. Sci. U. S. A. 90 (7), 2744 (1993).ADSCrossRefGoogle Scholar
  37. 37.
    D. R. Alexander, J. M. Hexham, and M. J. Crumpton, Biochem. J. 256, 885 (1988).CrossRefGoogle Scholar
  38. 38.
    K. C. Yeung, D. W. Rose, A. S. Dhillon, et al., Mol. Cell. Biol. 21 (21), 7207 (2001).CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Inc. 2018

Authors and Affiliations

  • A. S. Maiorov
    • 1
    • 2
    • 3
  • T. O. Shepelyuk
    • 1
    • 2
    • 3
    • 4
  • F. A. Balabin
    • 2
  • A. A. Martyanov
    • 1
    • 2
    • 3
  • D. Y. Nechipurenko
    • 1
    • 2
    • 3
    Email author
  • A. N. Sveshnikova
    • 1
    • 2
    • 3
  1. 1.Department of PhysicsMoscow State UniversityMoscowRussia
  2. 2.Center for Theoretical Problems of Physicochemical PharmacologyRussian Academy of SciencesMoscowRussia
  3. 3.National Medical Research Center of Pediatric Hematology, Oncology, and ImmunologyMoscowRussia
  4. 4.Faculty of Basic MedicineMoscow State UniversityMoscowRussia

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