Dataset Information

Maree2006_DuCa_Type1DiabetesModel

ABSTRACT: This a model from the article: Modelling the onset of Type 1 diabetes: can impaired macrophage phagocytosis make the difference between health and disease? Maree AF, Kublik R, Finegood DT, Edelstein-Keshet L.Philos Transact A Math Phys Eng Sci.2006 May 15;364(1842):1267-82. 16608707, Abstract: A wave of apoptosis (programmed cell death) occurs normally in pancreatic beta-cells of newborn mice. We previously showed that macrophages from non-obese diabetic (NOD) mice become activated more slowly and engulf apoptotic cells at a lower rate than macrophages from control (Balb/c) mice. It has been hypothesized that this low clearance could result in secondary necrosis, escalating inflammation and self-antigen presentation that later triggers autoimmune, Type 1 diabetes (T1D). We here investigate whether this hypothesis could offer a reasonable and parsimonious explanation for onset of T1D in NOD mice. We quantify variants of the Copenhagen model (Freiesleben De Blasio et al. 1999 Diabetes 48, 1677), based on parameters from NOD and Balb/c experimental data. We show that the original Copenhagen model fails to explain observed phenomena within a reasonable range of parameter values, predicting an unrealistic all-or-none disease occurrence for both strains. However, if we take into account that, in general, activated macrophages produce harmful cytokines only when engulfing necrotic (but not apoptotic) cells, then the revised model becomes qualitatively and quantitatively reasonable. Further, we show that known differences between NOD and Balb/c mouse macrophage kinetics are large enough to account for the fact that an apoptotic wave can trigger escalating inflammatory response in NOD, but not Balb/c mice. In Balb/c mice, macrophages clear the apoptotic wave so efficiently, that chronic inflammation is prevented. This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. For more information see the terms of use. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

DISEASE(S): Type 1 Diabetes Mellitus

SUBMITTER: Ishan Ajmera

PROVIDER: BIOMD0000000381 | BioModels | 2011-10-07

REPOSITORIES: BioModels

ACCESS DATA

Publications

Modelling the onset of Type 1 diabetes: can impaired macrophage phagocytosis make the difference between health and disease?

Marée Athanasius F M AF Kublik Richard R Finegood Diane T DT Edelstein-Keshet Leah L

Philosophical transactions. Series A, Mathematical, physical, and engineering sciences 20060501 1842

A wave of apoptosis (programmed cell death) occurs normally in pancreatic beta-cells of newborn mice. We previously showed that macrophages from non-obese diabetic (NOD) mice become activated more slowly and engulf apoptotic cells at a lower rate than macrophages from control (Balb/c) mice. It has been hypothesized that this low clearance could result in secondary necrosis, escalating inflammation and self-antigen presentation that later triggers autoimmune, Type 1 diabetes (T1D). We here invest ...[more]

PMID: 16608707

Publication: 1/2

Similar Datasets

Project description:Dunster2014 - WBC Interactions (Model1) This is a sub-model of a three-step inflammatory response modelling study. The model includes distinct populations of white blood cells namely, macrophages and active and apoptotic neutrophil populations. Neutrophil apoptosis rate is predicted to be crucial for the qualitative nature of the system. This model is described in the article: The resolution of inflammation: a mathematical model of neutrophil and macrophage interactions. Dunster JL, Byrne HM, King JR. Bull. Math. Biol. 2014 Aug; 76(8): 1953-1980 Abstract: There is growing interest in inflammation due to its involvement in many diverse medical conditions, including Alzheimer's disease, cancer, arthritis and asthma. The traditional view that resolution of inflammation is a passive process is now being superceded by an alternative hypothesis whereby its resolution is an active, anti-inflammatory process that can be manipulated therapeutically. This shift in mindset has stimulated a resurgence of interest in the biological mechanisms by which inflammation resolves. The anti-inflammatory processes central to the resolution of inflammation revolve around macrophages and are closely related to pro-inflammatory processes mediated by neutrophils and their ability to damage healthy tissue. We develop a spatially averaged model of inflammation centring on its resolution, accounting for populations of neutrophils and macrophages and incorporating both pro- and anti-inflammatory processes. Our ordinary differential equation model exhibits two outcomes that we relate to healthy and unhealthy states. We use bifurcation analysis to investigate how variation in the system parameters affects its outcome. We find that therapeutic manipulation of the rate of macrophage phagocytosis can aid in resolving inflammation but success is critically dependent on the rate of neutrophil apoptosis. Indeed our model predicts that an effective treatment protocol would take a dual approach, targeting macrophage phagocytosis alongside neutrophil apoptosis. This model is hosted on BioModels Database and identified by: BIOMD0000000616. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

Maree2006_DuCa_Type1DiabetesModel

Publications

Modelling the onset of Type 1 diabetes: can impaired macrophage phagocytosis make the difference between health and disease?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure