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Mathematical Modelling of Alternative Pathway of Complement System

The complement system (CS) is an integral part of innate immunity and can be activated via three different pathways. The alternative pathway (AP) has a central role in the function of the CS. The AP of complement system is implicated in several human disease pathologies. In the absence of triggers,...

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Autores principales: Bakshi, Suruchi, Cunningham, Fraser, Nichols, Eva-Maria, Biedzka-Sarek, Marta, Neisen, Jessica, Petit-Frere, Sebastien, Bessant, Christina, Bansal, Loveleena, Peletier, Lambertus A., Zamuner, Stefano, van der Graaf, Piet H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7024062/
https://www.ncbi.nlm.nih.gov/pubmed/32062771
http://dx.doi.org/10.1007/s11538-020-00708-z
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author Bakshi, Suruchi
Cunningham, Fraser
Nichols, Eva-Maria
Biedzka-Sarek, Marta
Neisen, Jessica
Petit-Frere, Sebastien
Bessant, Christina
Bansal, Loveleena
Peletier, Lambertus A.
Zamuner, Stefano
van der Graaf, Piet H.
author_facet Bakshi, Suruchi
Cunningham, Fraser
Nichols, Eva-Maria
Biedzka-Sarek, Marta
Neisen, Jessica
Petit-Frere, Sebastien
Bessant, Christina
Bansal, Loveleena
Peletier, Lambertus A.
Zamuner, Stefano
van der Graaf, Piet H.
author_sort Bakshi, Suruchi
collection PubMed
description The complement system (CS) is an integral part of innate immunity and can be activated via three different pathways. The alternative pathway (AP) has a central role in the function of the CS. The AP of complement system is implicated in several human disease pathologies. In the absence of triggers, the AP exists in a time-invariant resting state (physiological steady state). It is capable of rapid, potent and transient activation response upon challenge with a trigger. Previous models of AP have focused on the activation response. In order to understand the molecular machinery necessary for AP activation and regulation of a physiological steady state, we built parsimonious AP models using experimentally supported kinetic parameters. The models further allowed us to test quantitative roles played by negative and positive regulators of the pathway in order to test hypotheses regarding their mechanisms of action, thus providing more insight into the complex regulation of AP. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11538-020-00708-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-70240622020-03-13 Mathematical Modelling of Alternative Pathway of Complement System Bakshi, Suruchi Cunningham, Fraser Nichols, Eva-Maria Biedzka-Sarek, Marta Neisen, Jessica Petit-Frere, Sebastien Bessant, Christina Bansal, Loveleena Peletier, Lambertus A. Zamuner, Stefano van der Graaf, Piet H. Bull Math Biol Original Article The complement system (CS) is an integral part of innate immunity and can be activated via three different pathways. The alternative pathway (AP) has a central role in the function of the CS. The AP of complement system is implicated in several human disease pathologies. In the absence of triggers, the AP exists in a time-invariant resting state (physiological steady state). It is capable of rapid, potent and transient activation response upon challenge with a trigger. Previous models of AP have focused on the activation response. In order to understand the molecular machinery necessary for AP activation and regulation of a physiological steady state, we built parsimonious AP models using experimentally supported kinetic parameters. The models further allowed us to test quantitative roles played by negative and positive regulators of the pathway in order to test hypotheses regarding their mechanisms of action, thus providing more insight into the complex regulation of AP. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11538-020-00708-z) contains supplementary material, which is available to authorized users. Springer US 2020-02-15 2020 /pmc/articles/PMC7024062/ /pubmed/32062771 http://dx.doi.org/10.1007/s11538-020-00708-z Text en © The Author(s) 2020 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Bakshi, Suruchi
Cunningham, Fraser
Nichols, Eva-Maria
Biedzka-Sarek, Marta
Neisen, Jessica
Petit-Frere, Sebastien
Bessant, Christina
Bansal, Loveleena
Peletier, Lambertus A.
Zamuner, Stefano
van der Graaf, Piet H.
Mathematical Modelling of Alternative Pathway of Complement System
title Mathematical Modelling of Alternative Pathway of Complement System
title_full Mathematical Modelling of Alternative Pathway of Complement System
title_fullStr Mathematical Modelling of Alternative Pathway of Complement System
title_full_unstemmed Mathematical Modelling of Alternative Pathway of Complement System
title_short Mathematical Modelling of Alternative Pathway of Complement System
title_sort mathematical modelling of alternative pathway of complement system
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7024062/
https://www.ncbi.nlm.nih.gov/pubmed/32062771
http://dx.doi.org/10.1007/s11538-020-00708-z
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