Modeling of an immune response: Queuing network analysis of the impact of zinc and cadmium on macrophage activation

Abstract

Chronic obstructive pulmonary disease is characterized by progressive, irreversible airflow obstruction resulting from an abnormal inflammatory response to noxious gases and particles. Alveolar macrophages rely on the transcription factors, nuclear factor κB and mitogen-activated protein kinase, among others, to facilitate the production of inflammatory mediators designed to help rid the lung of foreign pathogens and noxious stimuli. Building a kinetic model using queuing networks, provides a quantitative approach incorporating an initial number of individual molecules along with rates of the reactions in any given pathway. Accordingly, this model has been shown useful to model cell behavior including signal transduction, transcription, and metabolic pathways. The aim of this study was to determine whether a queuing theory model that involves lipopolysaccharide-mediated macrophage activation in tandem with changes in intracellular Cd and zinc (Zn) content or a lack thereof, would be useful to predict their impact on immune activation. We then validate our model with biologic cytokine output from human macrophages relative to the timing of innate immune activation. We believe that our results further prove the validity of the queuing theory approach to model intracellular molecular signaling and postulate that it can be useful to predict additional cell signaling pathways and the corresponding biological outcomes.

Modeling an immune response to influenza A virus infection in alveolar epithelial cells

“…The values were obtained from previous models and literature. Research studies and models that were the most helpful were (Loo & Gale, 2011; Nitz et al, 2020; Solis et al, 2007; Zhang et al, 2012). When the initial concentration of a protein or the kinetic constant of a reaction could not be determined or found from existing research, the parameter was estimated by multiplying a similar known parameter value by the molecular mass ratio of the known parameter protein and the unknown parameter protein.…”

“…The MATLAB ® script used to run simulations and generate results can be found using the following link (https://gist.github.com/ mlmiller8/2405a7c70f7175bd54d86a9edbce2583). The detailed mathematical description of a basic queue used in the model can be found in (Nitz et al, 2020).…”

“…Research studies and models that were the most helpful were (Loo & Gale, 2011;Nitz et al, 2020;Solis et al, 2007;Zhang et al, 2012).…”

Supervised-learning-based approximation method for multi-server queueing networks under different service disciplines with correlated interarrival and service times

“…Queueing networks have been used in modeling a wide range of systems including manufacturing systems, transportation networks, health care facilities and biochemical processes (Jiang and Giachetti 2008, Zhang and Pavone 2016, Fan et al 2020, Nitz et al 2021).…”