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dc.contributor.authorWilliams, Robert Jowers
dc.description.abstractThe heavy metal lead (Pb) is a persistent environmental pollutant that does not breakdown over time like other chemicals. Acute and chronic exposure to Pb can cause severe toxicities in numerous organ systems. Avian species are susceptible to exposure from numerous forms of Pb in the environment including spent Pb ammunition. While it is known that Pb can cause multi-organ toxicities in the developing birds, there are limited data demonstrating the role of maternal Pb in the developing offspring. Hen roller pigeons were exposed to a single Pb pellet commonly deposited in the environment through recreational shooting and allowed to mate. Egg production and size, hatchling initial weight and final weight, blood analysis, and organ collection were all conducted to determine maternal Pb impact on F1 development. These data showed that eggs and progeny of the first clutch were significantly smaller than unexposed hens. Further histologic analysis indicated that Pb significantly altered the development of the thymus and spleen in progeny months following exposure. These data demonstrate that developmental exposure to Pb can cause immune suppression in avian species. Given these data and previous knowledge, the pro-inflammatory response of macrophages exposed to Pb was investigated using the RAW 264.7 cell line and an environmentally relevant concentration of Pb (5μM Pb(NO3)2). These cells were induced towards a pro-inflammatory state using a bacterial antigen and select cytokine alone or in combination. Western blot data showed that initial exposure to Pb altered cytoplasmic protein signaling in calcium pathways as well as key pro-inflammatory pathways. Functional assays showed that cellular proliferation, nitric oxide production, and cytokine expression were significantly altered in the Pb exposed cells. These data offer a new mechanism for macrophage pro-inflammatory inhibition by Pb. These data also suggest a potential mechanism for macrophage further driving Pb induced Th2 cells towards anti-inflammatory functional response resulting in the Th2 immune profiles presented in chronic Pb exposure.
dc.subjectProtein Signaling
dc.titleReproductive and developmental lead toxicity in roller pigeons and an investigation of lead nitrate impact on inflammatory response and calcium signaling in a mammalian macrophage cell line
dc.description.departmentVeterinary and Biomedical Sciences
dc.description.advisorRobert Gogal, Jr.
dc.description.committeeRobert Gogal, Jr.
dc.description.committeeJia-Sheng Wang
dc.description.committeeSteven Holladay
dc.description.committeeR. Jeff Hogan
dc.description.committeeTai Guo

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