Platelet-driven routes to chaos in a model of hepatitis

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Nelson, M. R., Gibbins, J. M. ORCID: https://orcid.org/0000-0002-0372-5352 and Dunster, J. L. ORCID: https://orcid.org/0000-0001-8986-4902 (2023) Platelet-driven routes to chaos in a model of hepatitis. Chaos, Solitons & Fractals, 170. 113338. ISSN 1873-2887 doi: 10.1016/j.chaos.2023.113338

Abstract/Summary

Hepatitis is a general term used to describe inflammation in the liver, the regulation of which involves a complex array of interactions between liver cells, inflammatory mediators and cells of the immune system (macrophages and neutrophils, in particular). There is increasing evidence that platelets (small blood cells that are primarily responsible for clotting) affect numerous mechanisms that underlie hepatitis, including the rates of cell migration, liver damage and mediator production, giving rise to a complex and diverse range of inflammatory outcomes. In particular, platelet activation has the scope to promote both healthy and chronic outcomes in a highly unpredictable and potentially state-dependent manner that is not currently well-understood. In this paper, we take an existing model of the inflammatory dynamics associated with hepatitis, and introduce platelets and their effects. We interrogate this new model via numerical simulations in Matlab and bifurcation analysis in XPPAUT, and find that amplification of certain key interactions by platelets can stimulate chaotic dynamics that correspond to complex chronic outcomes. We initially introduce a single parameter to represent the scale of the platelet stimulus and, through bifurcation analysis, illustrate that as this parameter is gradually increased we see the emergence of a period-doubling cascade that results in chaotic dynamics. We then explore individual mechanisms in more detail and illustrate that, while neutrophils can promote chaos in some settings, routes to chaos are primarily driven by macrophage- related platelet stimuli. Finally, we briefly comment upon the implications of our observations in terms of the ongoing hunt for new therapeutic interventions in hepatitis, as well as other inflammation-related medical conditions.

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Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/111062
Item Type	Article
Refereed	Yes
Divisions	Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR) Life Sciences > School of Biological Sciences > Biomedical Sciences
Uncontrolled Keywords	hepatitis, chaos, platelets, period doubling, inflammation
Publisher	Elsevier
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Date Deposited:	17 Mar 2023 11:10	Date item deposited into CentAUR
Last Modified:	30 Jun 2024 01:06	Date item last modified

References

[1] C. Deppermann, P. Kubes, Start a fire, kill the bug: The role of platelets in inflammation and infection, Innate Immunity 24 (6) (2018) 335–348. [2] H. Chen, X. Chen, G. Wang, Platelets: a review of their function and effects in liver diseases, Liver Research 4 (3) (2020) 129–135. [3] T. Lisman, J. P. Luyendyk, Platelets as modulators of liver diseases, in: Seminars in thrombosis and hemostasis, Vol. 44(2), Thieme Medical Publishers, 2018, pp. 114–125. [4] A. Chauhan, D. H. Adams, S. P. Watson, P. F. Lalor, Platelets: No longer bystanders in liver disease, Hepatology 64 (5) (2016) 1774–1784. [5] J. L. Dunster, J. M. Gibbins, M. R. Nelson, Exploring the constituent mechanisms of hepatitis: a dynamical systems approach, Mathematical Medicine and Biology: A Journal of the IMA (2022) dqac013. [6] D. L. Gandy, M. R. Nelson, Analysing pattern formation in the Gray-Scott model: an XPPAUT tutorial, SIAM Review 64 (3) (2022) 728–747. [7] I.Slaba,J.Wang,E.Kolaczkowska,B.McDonald,W.-Y.Lee,P.Kubes,Imagingthedynamicplatelet-neutrophilresponse in sterile liver injury and repair in mice, Hepatology 62 (5) (2015) 1593–1605. [8] J. Rossaint, A. Margraf, A. Zarbock, Role of platelets in leukocyte recruitment and resolution of inflammation, Frontiers in immunology 9 (2018) 2712. [9] S.Gudbrandsdottir,H.C.Hasselbalch,C.H.Nielsen,Activatedplateletsenhanceil-10secretionandreducetnf-αsecretion by monocytes, The Journal of Immunology 191 (8) (2013) 4059–4067. [10] S. Yoshida, N. Ikenaga, S. B. Liu, Z.-W. Peng, J. Chung, D. Y. Sverdlov, M. Miyamoto, Y. O. Kim, S. Ogawa, R. H. Arch, et al., Extrahepatic platelet-derived growth factor-β, delivered by platelets, promotes activation of hepatic stellate cells and biliary fibrosis in mice, Gastroenterology 147 (6) (2014) 1378–1392. [11] B. Xiang, G. Zhang, L. Guo, X.-A. Li, A. J. Morris, A. Daugherty, S. W. Whiteheart, S. S. Smyth, Z. Li, Platelets protect from septic shock by inhibiting macrophage-dependent inflammation via the cyclooxygenase 1 signalling pathway, Nature communications 4 (1) (2013) 1–12. [12] C. N. Jenne, P. Kubes, Platelets in inflammation and infection, Platelets 26 (4) (2015) 286–292. [13] J. L. Dunster, H. M. Byrne, J. R. King, The resolution of inflammation: a mathematical model of neutrophil and macrophage interactions, Bulletin of Mathematical Biology 76 (2014) 1953–1980. [14] A. Bayani, J. L. Dunster, J. J. Crofts, M. R. Nelson, Mechanisms and points of control in the spread of inflammation: a mathematical investigation, Bulletin of Mathematical Biology 82 (4) (2020) 1–22. [15] P. Ramadori, T. Klag, N. P. Malek, M. Heikenwalder, Platelets in chronic liver disease, from bench to bedside, JHEP Reports 1 (6) (2019) 448–459. [16] B. Rius, C. L ́opez-Vicario, A. Gonz ́alez-P ́eriz, E. Mor ́an-Salvador, V. Garc ́ıa-Alonso, J. Cl`aria, E. Titos, Resolution of inflammation in obesity-induced liver disease, Frontiers in immunology 3 (2012) 257. [17] S. Watanabe, M. Alexander, A. V. Misharin, G. S. Budinger, et al., The role of macrophages in the resolution of inflam- mation, The Journal of clinical investigation 129 (7) (2019) 2619–2628. [18] D. van der Heide, R. Weiskirchen, R. Bansal, Therapeutic targeting of hepatic macrophages for the treatment of liver diseases, Frontiers in immunology 10 (2019) 2852. [19] P. Kanikarla Marie, N. W. Fowlkes, V. Afshar-Kharghan, S. L. Martch, A. Sorokin, J. P. Shen, V. K. Morris, A. Dasari, N. You, A. K. Sood, et al., The provocative roles of platelets in liver disease and cancer, Frontiers in Oncology (2021) 2802. [20] G. P. Langlois, M. Craig, A. R. Humphries, M. C. Mackey, J. M. Mahaffy, J. B ́elair, T. Moulin, S. R. Sinclair, L. Wang, Normal and pathological dynamics of platelets in humans, Journal of Mathematical Biology 75 (6) (2017) 1411–1462. [21] O. Mitchell, D. M. Feldman, M. Diakow, S. H. Sigal, The pathophysiology of thrombocytopenia in chronic liver disease, Hepatic medicine: evidence and research 8 (2016) 39. [22] J. B ́elair, M. C. Mackey, A model for the regulation of mammalian platelet production, Annals of the New York Academy of Sciences 504 (1987) 280–282. [23] G. V. Fisher, An introduction to chaos theory and some haematological applications, Comparative Haematology Interna- tional 3 (1) (1993) 43–51. [24] M. C. Mackey, L. Glass, Oscillation and chaos in physiological control systems, Science 197 (4300) (1977) 287–289. [25] A. Bayani, J. L. Dunster, J. J. Crofts, M. R. Nelson, Spatial considerations in the resolution of inflammation: Elucidating leukocyte interactions via an experimentally-calibrated agent-based model, PLOS Computational Biology 16 (11) (2020) e1008413. [26] M. B. Hilscher, T. Sehrawat, J. P. Arab, Z. Zeng, J. Gao, M. Liu, E. Kostallari, Y. Gao, D. A. Simonetto, U. Yaqoob, et al., Mechanical stretch increases expression of cxcl1 in liver sinusoidal endothelial cells to recruit neutrophils, generate sinusoidal microthombi, and promote portal hypertension, Gastroenterology 157 (1) (2019) 193–209. [27] Y. Koyama, D. A. Brenner, Liver inflammation and fibrosis, The Journal of clinical investigation 127 (1) (2017) 55–64. [28] M. Tanaka, A. Miyajima, Liver regeneration and fibrosis after inflammation, Inflammation and Regeneration 36 (1) (2016) 1–6.

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