A systematic evaluation of the influence of macrophage phenotype descriptions on inflammatory dynamics.

Autor:	Almansour S; School of Science & Technology, Nottingham Trent University, Nottingham, NG11 8NS, UK., Dunster JL; Institute for Cardiovascular and Metabolic Research, University of Reading, Reading, RG6 6AS, UK., Crofts JJ; School of Science & Technology, Nottingham Trent University, Nottingham, NG11 8NS, UK., Nelson MR; School of Science & Technology, Nottingham Trent University, Nottingham, NG11 8NS, UK.
Jazyk:	angličtina
Zdroj:	Mathematical medicine and biology : a journal of the IMA [Math Med Biol] 2024 Jun 15; Vol. 41 (2), pp. 81-109.
DOI:	10.1093/imammb/dqae004
Abstrakt:	Macrophages play a wide range of roles in resolving the inflammatory damage that underlies many medical conditions and have the ability to adopt different phenotypes in response to different environmental stimuli. Categorising macrophage phenotypes exactly is a difficult task, and there is disparity in the literature around the optimal nomenclature to describe these phenotypes; however, what is clear is that macrophages can exhibit both pro- and anti-inflammatory behaviours dependent upon their phenotype, rendering mathematical models of the inflammatory response potentially sensitive to their description of the macrophage populations that they incorporate. Many previous models of inflammation include a single macrophage population with both pro- and anti-inflammatory functions. Here, we build upon these existing models to include explicit descriptions of distinct macrophage phenotypes and examine the extent to which this influences the inflammatory dynamics that the models emit. We analyse our models via numerical simulation in MATLAB and dynamical systems analysis in XPPAUT, and show that models that account for distinct macrophage phenotypes separately can offer more realistic steady state solutions than precursor models do (better capturing the anti-inflammatory activity of tissue resident macrophages), as well as oscillatory dynamics not previously observed. Finally, we reflect on the conclusions of our analysis in the context of the ongoing hunt for potential new therapies for inflammatory conditions, highlighting manipulation of macrophage polarisation states as a potential therapeutic target. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.)
Databáze:	MEDLINE
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