Modelling the continuum of macrophage phenotypes and their role in inflammation.

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. Electronic address: Martin.Nelson@ntu.ac.uk.
Jazyk: angličtina
Zdroj: Mathematical biosciences [Math Biosci] 2024 Nov; Vol. 377, pp. 109289. Date of Electronic Publication: 2024 Sep 05.
DOI: 10.1016/j.mbs.2024.109289
Abstrakt: Macrophages are a type of white blood cell that play a significant role in determining the inflammatory response associated with a wide range of medical conditions. They are highly plastic, having the capacity to adopt numerous polarisation states or 'phenotypes' with disparate pro- or anti-inflammatory roles. Many previous studies divide macrophages into two categorisations: M1 macrophages are largely pro-inflammatory in nature, while M2 macrophages are largely restorative. However, there is a growing body of evidence that the M1 and M2 classifications represent the extremes of a much broader spectrum of phenotypes, and that intermediate phenotypes can play important roles in the progression or treatment of many medical conditions. In this article, we present a model of macrophage dynamics that includes a continuous description of phenotype, and hence incorporates intermediate phenotype configurations. We describe macrophage phenotype switching via nonlinear convective flux terms that scale with background levels of generic pro- and anti-inflammatory mediators. Through numerical simulation and bifurcation analysis, we unravel the model's resulting dynamics, paying close attention to the system's multistability and the extent to which key macrophage-mediator interactions provide bifurcations that act as switches between chronic states and restoration of health. We show that interactions that promote M1-like phenotypes generally result in a greater array of stable chronic states, while interactions that promote M2-like phenotypes can promote restoration of health. Additionally, our model admits oscillatory solutions reminiscent of relapsing-remitting conditions, with macrophages being largely polarised toward anti-inflammatory activity during remission, but with intermediate phenotypes playing a role in inflammatory flare-ups. We conclude by reflecting on our observations in the context of the ongoing pursuance of novel therapeutic interventions.
Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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