Date of Award

2013-01-01

Degree Name

Doctor of Philosophy

Department

Biological Sciences

Advisor(s)

Kristine M. Garza

Second Advisor

JianYing Zhang

Abstract

Obesity is a complex, chronic disease that has reached epidemic proportions in the United States and shows no indication of receding. It is a state of chronic low-grade inflammation that is initiated by morphological changes in large accumulations of adipose tissue. Leptin is a pleiotropic hormone secreted by adipose tissue, presenting a possible link between obesity and inflammation. In this study, we assessed the effect of leptin on bone marrow-derived (BM) dendritic cells (DC) (BM-DC) function, antigen presenting cells vital for the activation of naí¯ve T cells. Previous data produced in our laboratory established that the addition of leptin to BM-DC causes cytoskeletal rearrangement resulting in an increased number, circumference, and length of llamelopodia/dendrites. We hypothesized that leptin treatment would therefore lead to an increased capacity of DC to migrate to, to interact with, and to activate T cells. Leptin-treated BM-DC functionality was evaluated in vitro using transwell migration assays in response to a DC-specific chemokine; by flow cytometry to measure the percentage of BM-DC and T cell interactions; by confocal microscopy to determine the number of T cells interacting with individual BM-DC; and by measuring activation of antigen-specific T cells. Treatment with leptin enhanced all measurements of BM-DC function relative to untreated controls. This is likely due to the increased surface area (dendrite number and length), which increased DC ability to diapedese and to interact with T cells, therefore potentiating the extent of the physical contact between these cells. The data obtained from this study suggest leptin plays an important role in immunological responses, and may specifically contribute to the pro-inflammatory state found in obesity.

Language

en

Provenance

Received from ProQuest

File Size

66 pages

File Format

application/pdf

Rights Holder

Amanda L. Gonzales

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