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.
Similar content being viewed by others
Abbreviations
- LPS:
-
lipopolysaccharide(s)
- TLR:
-
toll-like receptor
- LBP:
-
LPS-binding protein (the plasma protein that binds LPS and delivers it to the CD14 protein)
References
A. D. Michelson, Platelets (Elsevier, 2013).
G. Zhang, J. Han, E. J. Welchet, et al., J. Immunol. 182 (12), 7997 (2009).
G. Andonegui, S. M. Kerfoot, K. McNagny, et al., Blood 106 (7), 2417 (2005).
V. Matus, J. G. Valenzuela, P. Hidalgo, et al., PLoS One 4, 1 (2017).
A. L. Ståhl, M. Svensson, M. Mörgelin, et al., Blood 108 (1), 167 (2006).
N. E. Gomes, M. K. C. Brunialti, M. E. Mendes, et al., Braz. J. Med. Biol. Res. 43, 853 (2010).
S. Akira and K. Takeda, Nat. Rev. Immunol. 4, 499 (2004).
G. Andonegui, S. M. Kerfoot, K. McNagny, et al., Blood 106, 2417 (2005).
E. Ampofo, I. Müller, I. N. Dahmke, et al., Thromb. Res. 136, 996 (2015).
R. Aslam, E. R. Speck, M. Kim, et al., Blood 107, 637 (2006). doi 10.1182/blood-2005-06-2202
G. C. Sharp, H. Ma, P. T. K. Saunders, and J. E. Norman, PLoS One 8 (7), e70180 (2013).
F. Rendu and B. Brohard-Bohn, Platelets 12, 261 (2001).
M. H. Fukami, J. S. Bauer, G. J. Stewart, and L. Salganicoff, J. Cell Biol. 77, 389 (1978).
S. Vogel, R. Bodenstein, Q. Chen, et al., J. Clin. Invest. 125 (12), 4638 (2015).
X. Yang, H. Wang, M. Zhang, et al., Diagn. Pathol. 10, 134 (2015).
L. Petzold and A. Hindmarsh, LSODA: Livermore Solver of Ordinary Differential Equations (Lawrence Livermore National Laboratory, Livermore, CA, 1997).
A. C. Hindmarsh, ACM Signum Newsl. 15, 10 (1980).
P. Mendes, S. Hoops, S. Sahle, et al., Methods Mol. Biol. 500, 17 (2009).
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.
J. Berthet, P. Damien, H. Hamzeh-Cognasse, et al., Br. J. Haematol. 151 (1), 89 (2010).
B. S. Park, D. H. Song, H. M. Kim, et al., Nature 458, 1191 (2009).
H. J. Shin, H. Lee, J. D. Park, et al., Mol. Cells 24 (1), 119 (2007).
L. A. Ryan, J. Zheng, M. Brester, et al., J. Infect. Dis. 184 (6), 699 (2017).
E. Hailman, T. Vasselon, M. Kelley, et al., J. Immunol. 156, 4384 (1996).
T. Kusunoki, S. D. Wright, Y. Inoue, and T. Miyanomae, Allergol. Int. 47, 271 (1998).
P. G. Motshwene, M. C. Moncrieffe, J. G. Grossmann, et al., J. Biol. Chem. 284, 25404 (2009).
S.-C. Lin, Y.-C. Lo, and H. Wu, Nature 465, 885 (2010).
H. Wu and J. R. Arron, BioEssays 25, 109605 (2003).
C. W. Philipson, J. Bassaganya-Riera, M. Viladomiu, et al., PLoS One 10, e0137839 (2015).
L. Deng, Ch. Wang, E. Spencer, et al., Cell 103, 351 (2000).
J. Napetschnig and H. Wu, Annu. Rev. Biophys. 42, 443 (2013).
Z. A. Karim, J. Zhang, M. Banerjee, et al., Blood 121 (22), 4567 (2016).
R. D. Moriarty, A. Cox, M. McCall, et al., J. Thromb. Haemost. 14, 797 (2016).
C. N. Watson, S. W. Kerrigan, D. Cox, et al., Platelets 7104, 1 (2016).
J. M. Burkhart, M. Vaudel, S. Gambaryan, et al., Blood 120, e73 (2012).
J. Pugin, C. C. Schürer-Maly, D. Leturcq, et al., Proc. Natl. Acad. Sci. U. S. A. 90 (7), 2744 (1993).
D. R. Alexander, J. M. Hexham, and M. J. Crumpton, Biochem. J. 256, 885 (1988).
K. C. Yeung, D. W. Rose, A. S. Dhillon, et al., Mol. Cell. Biol. 21 (21), 7207 (2001).
Author information
Authors and Affiliations
Corresponding author
Additional information
Original Russian Text © A.S. Maiorov, T.O. Shepelyuk, F.A. Balabin, A.A. Martyanov, D.Y. Nechipurenko, A.N. Sveshnikova, 2018, published in Biofizika, 2018, Vol. 63, No. 3, pp. 475–483.
Rights and permissions
About this article
Cite this article
Maiorov, A.S., Shepelyuk, T.O., Balabin, F.A. et al. Modeling of Granule Secretion upon Platelet Activation through the TLR4-Receptor. BIOPHYSICS 63, 357–364 (2018). https://doi.org/10.1134/S0006350918030144
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S0006350918030144