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Proposed in vitro model of neutrophil swarming in a chronic, low-level inflammatory state

Chronic, low-grade inflammation is an underlying condition across a globally increasing number of debilitating diseases. These diseases include obesity, atherosclerosis, and diabetes and their resultant low-grade inflammation can be effectivity modeled with low dose stimulants such as lipopolysaccharide (LPS). While the innate immunity plays a significant role in fighting infectious disease, an initial exposure to low dose LPS hinders secondary infection clearance and pre-disposes murine models for fatal sepsis. Neutrophils are the most prevalent circulating innate immune cell and their homotypic aggregation, or swarming, is a key mechanism in clearing pathogens greater than 20 μm in size. We hypothesize that neutrophil swarming ability is altered when in a low dose LPS primed state; potentially leading to an overall altered innate immune response in the face of infection. However, an in vitro model does not currently exist to reliably quantify and compare neutrophil swarms across treatment groups. Here we propose a novel model utilizing fungal zymosan coated beads as a uniform target to which neutrophils may swarm. / Master of Science / White blood cells are critical for our body’s ability to fight off infection. The pathogens that cause infections come in many forms including fungus, viruses, and bacteria. However, in many debilitating inflammatory diseases such as heart disease and obesity, chronic inflammation prevents one’s white blood cells from being able to properly fight off infection. In order to study white blood cell function without the variability that is analogous to living pathogens, we propose a model system that simulates an artificial pathogen target where both the target and the surrounding environment can be precisely controlled. This system can then be used to study white blood cell function, specifically how it may be impacted under inflammatory conditions.

Identiferoai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/102737
Date24 September 2019
CreatorsBradford, Elaine Alison
ContributorsBiological Sciences, Li, Liwu, Jones, Caroline N., Zhang, Yao
PublisherVirginia Tech
Source SetsVirginia Tech Theses and Dissertation
Detected LanguageEnglish
TypeThesis
FormatETD, application/pdf, application/pdf, application/pdf
RightsIn Copyright, http://rightsstatements.org/vocab/InC/1.0/

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