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Bakshi2020 - Properdin model of alternative pathway of complement system


ABSTRACT: This model is based on the publication: "Mathematical Modelling of Alternative Pathway of Complement System". 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 DOI: 10.1007/s11538-020-00708-z Comment: This model is based on the properdin model equations (Eq. C.1) from the manuscript. Reproduction of Fig. 5 was achieved by setting d4 = 1.6e-4, different to the value quoted in the article. N.B.: Eq. C.1 is inconsistent with the schematic diagram (Fig. 3) in manuscrpt. The author has clarified that the schematic representation is correct, i.e. k4 and k5 should be involved with the reaction concerning C3bBP_closed (rather than C3bBP_open). The authors used uncorrected Eq. C.1 to produce Fig. 5, hence the uncorrected equations were used to curate this model and reproduce Fig. 5 from the manuscript. The corrected versions of the equations being discussed from the Eq. C.1 set are as follows: dFB/dt = ks2 - d2*FB - k4*FB(C3b + C3bP) + k5(C3bB_closed + C3bBP_closed) dC3bBP_closed/dt = k23*C3bB_closed*P - k14*C3bBP_closed - k9*C3bBP_closed + k10*C3bBP_open + k4*C3bP*FB - k5*C3bBP_closed dC3bBP_open/dt = k24*C3bB_open*P - k14*C3bBP_open + k9*C3bBP_closed - k10*C3bBP_open - (k7*FD*C3bBP_open)/(k8 + C3bB_open + C3bBP_open) Abstract: 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.

SUBMITTER: Emilia Chen  

PROVIDER: BIOMD0000001018 | BioModels | 2021-07-20

REPOSITORIES: BioModels

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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  ...[more]

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