Master defence by Rógvi Dávid Arge – Niels Bohr Institute - University of Copenhagen

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Niels Bohr Institute > Calendar > NBI Calendar 2015 > Master defence by Rógv...

Master defence by Rógvi Dávid Arge

Abstract:

The pro-inflammatory cytokines interferon-gamma, TNF-alpha and Interleukin-1-beta are an essential part of macrophage polarization and of the inflammatory response in macrophages. Macrophages remove cellular debris, foreign substances and microbes in a process called phagocytosis, and are a vital part of the immune system. However, for various unknown reasons, the inflammatory response can get activated by substances and tissue normally present in the body, which in many cases leads to chronic inflammation. This is the case in multiple sclerosis (MS), a so called autoimmune disease, in which macrophages remove the isolating myelin-layer from axons in the central nervous system (CNS), resulting in plaques.

In this thesis I focus on pro-inflammatory macrophages, the activation of Nuclear Factor-kappa B, and the chemotactic movement of macrophages. I apply and modify a model previously developed for the inflammatory response in neutrophils to fit a system of macrophages. Furthermore, I introduce macrophage motility.

Based on simulations I show that macrophages can accumulate into plaques, and that the number of plaques and their size depends on the diffusion constant, the parameter p, and the number of macrophages. I find a linear relation between the diffusion constant and the average plaque size, when $p$ is low, as well as a linear relation between the average plaque size and the number of macrophages, when $p$ is high. Furthermore I show that there is a qualitative differences between a low $p$ system and a high $p$ system. Inspired by the study by starossom et al. which shows that plaques can be resolved by introducing GAL1, an inhibitor of the \nfkb{} activation, I also show possible ways one could resolve plaques through \nfkb{} activator inhibition or cytokine inhibition.

Supervisor: Mogens Høgh Jensen