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 Title: The macrophage activating properties of growth hormone in vitro and in vivo: Comparison to interferon-gamma (IF N-gamma) Author(s): Edwards, Carl Keith, III Doctoral Committee Chair(s): Kelley, Keith W. Department / Program: Animal Sciences Discipline: Animal Sciences Degree Granting Institution: University of Illinois at Urbana-Champaign Degree: Ph.D. Genre: Dissertation Subject(s): Health Sciences, Immunology Abstract: Macrophages (M$\Phi$) elicited by injections of inflammatory agents or obtained from animals infected with intracellular parasites are primed so that they respond to phagocytosis of opsonized particles such as opsonized-zymosan (Op-zym) with a marked increase in the respiratory burst, NADPH oxidase system. This capacity to increase the release of reactive oxygen metabolites, including superoxide anion (O$\sb2\sp-$), plays an important role in the enhanced microbicidal capacity of activated M$\Phi$. To date, Interferon-$\gamma$ (IFN-$\gamma$), a classically defined macrophage activating factor (MAF), has been the most completely characterized substance both in vitro and in vivo known to be produced by mammalian cells that augments the production of reactive oxygen metabolites, including O$\sb2\sp-$, by M$\Phi$. Other MAF-like molecules such as Interleukin-4 and Granulocyte/Macrophage Colony Stimulating Factor are thought to exist. Growth hormone (GH) is synthesized by the adenohypophysis, and it has also been shown to be produced by activated lymphoid cells. Therefore, the role of GH in regulating M$\Phi$ activation has been addressed in this dissertation. Data are presented which provide the first evidence that GH augments the production of O$\sb2\sp-$ by mononuclear phagocytes in vitro and in vivo. When either native or recombinant GH were administered to hypophysectomized rats in vivo, activation of peritoneal M$\Phi$, as measured by O$\sb2\sp-$ release, was equivalent to that of M$\Phi$ from rats primed with IFN-$\gamma$. Because M$\Phi$ are capable of exerting antimicrobial activities toward intracellular pathogens through an enhanced respiratory burst in vitro and in vivo, data are presented which indicate that rats treated with IFN-$\gamma$ or GH have enhanced resistance to a Salmonella typhimurium infection over a 14-day period and this resistance was due in-part to the generation of reactive oxygen intermediates. Since it is important to know whether GH augments other M$\Phi$ functional activities, other studies address the ability of IFN-$\gamma$ or GH administered to hypophysectomized rats in vivo to up-regulate the cytokine Tumor Necrosis Factor-$\alpha$. The biological relevance of this observation is demonstrated by showing that in vivo priming of endotoxin induced hemorrhagic necrosis of murine tumors in mice can be mediated by IFN-$\gamma$ and GH. In summary, the data presented in these experiments suggest that GH plays an important "cytokine-like" role in regulating M$\Phi$ functional activities in vitro and in vivo. Issue Date: 1989 Type: Text Language: English URI: http://hdl.handle.net/2142/20534 Rights Information: Copyright 1989 Edwards, Carl Keith, III Date Available in IDEALS: 2011-05-07 Identifier in Online Catalog: AAI8924810 OCLC Identifier: (UMI)AAI8924810
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