Mathematical Modelling of Alternative Pathway of Complement System

被引:0
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作者
Suruchi Bakshi
Fraser Cunningham
Eva-Maria Nichols
Marta Biedzka-Sarek
Jessica Neisen
Sebastien Petit-Frere
Christina Bessant
Loveleena Bansal
Lambertus A. Peletier
Stefano Zamuner
Piet H. van der Graaf
机构
[1] Leiden University,Division of Systems Biomedicine and Pharmacology, LACDR
[2] Certara QSP,Cytokine, Chemokine and Complement DPU, Immunoinflammation TA Unit
[3] GSK,Computational and Modelling Sciences, Platform Technology Sciences
[4] GSK,Mathematical Institute
[5] Leiden University,Clinical Pharmacology, Modelling and Simulation
[6] GSK,undefined
[7] Certara QSP,undefined
来源
Bulletin of Mathematical Biology | 2020年 / 82卷
关键词
Alternative pathway; Complement system; Immunology; C3 glomerulopathy;
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摘要
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.
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