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Innate Immune Cell Phenotypes Are Dictated By Distinct Epigenetic Reprogramming, Kevin Douglas Adams Dec 2018

Innate Immune Cell Phenotypes Are Dictated By Distinct Epigenetic Reprogramming, Kevin Douglas Adams

Theses and Dissertations

The innate immune system is the first line of host defense against external exposures. During these initial encounters, antigen presenting cells - specifically monocytes and macrophages - modulate further inflammatory responses. Macrophages exist along a spectrum of phenotypic programs; on the inflammatory M1 end they enhance immune activity while on the anti-inflammatory M2 end they suppress further immune activation. Furthermore, within M2 macrophages there exist many subpopulations, namely M2a and M2d, each with specific roles during infection or exposure. We sought to compare the epigenetic profiles of these subpopulations of macrophages to determine key regulatory gene networks and factors that …


Impact Of Aerobic Exercise On Monocyte Subset Receptor Expression And Macrophage Polarization, Anson M. Blanks Jan 2018

Impact Of Aerobic Exercise On Monocyte Subset Receptor Expression And Macrophage Polarization, Anson M. Blanks

Theses and Dissertations

Atherosclerotic cardiovascular disease (CVD) is hallmarked by inflammatory immune activation, particularly by the induction of a response by monocytes. Classical (CD14++CD16-) are anti-inflammatory mediators under homeostatic conditions, while intermediate (CD14++CD16+) and non-classical (CD14LowCD16++) monocytes promote inflammation following activation. Monocyte activation and functionality is dependent upon receptor expression and ligand production by a variety of cells, including monocytes. Alterations in the expression of surface receptors often have a direct impact upon monocyte function, such as the increased pro-inflammatory cytokine production in response to activation that accompanies elevated CD14 expression …


The Pro-Inflammatory Contributions Of Receptors For Advanced Glycation End-Products (Rage) In Alveolar Macrophages Following Cigarette Smoke Exposure, Adam Benjamin Robinson Jun 2012

The Pro-Inflammatory Contributions Of Receptors For Advanced Glycation End-Products (Rage) In Alveolar Macrophages Following Cigarette Smoke Exposure, Adam Benjamin Robinson

Theses and Dissertations

Receptors for advanced glycation end-products (RAGE) are multi-ligand cell surface receptors of the immunoglobin family expressed by epithelium and macrophages. RAGE expression increases following ligand binding and when diverse cells are exposed to a variety of insults including cigarette smoke extract (CSE). The current research sought to characterize the pro-inflammatory contributions of RAGE expressed by alveolar macrophages (AMs) following CSE exposure. Acute exposure of mice to CSE via nasal instillation revealed diminished bronchoalveolar lavage (BAL) cellularity and fewer AMs in RAGE null mice compared to controls. Primary AMs were obtained from BAL, exposed to CSE in vitro, and RNA, DNA, …


The Regulation Of Platelet Activating Factor Acetylhydrolase By Oxidized Phospholipids, Rachael Griffiths Jul 2009

The Regulation Of Platelet Activating Factor Acetylhydrolase By Oxidized Phospholipids, Rachael Griffiths

Theses and Dissertations

Platelet-activating factor acetylhydrolase (PAFAH) is elevated in atherosclerosis and may play a role in pathogenesis of this disease. Molecular mechanisms regulating the expression of this lipoprotein-associated PLA2 are indistinct. Mildy oxidized low density lipoprotein (oxLDL) and monocytes (the primary source of PAFAH) are co-localized in early atheromas. Monocytes are activated by oxidized phospholipids (oxPL) in the oxLDL particle. We hypothesized that oxPL-activated monocytes are the source of increased levels of PAFAH in atherosclerosis. We found that PAFAH expression is significantly induced by OxPAPC and in particular long-chain fractions of oxPAPC in monocytes and cytokine-differentiated DC, but not cytokine-differentiated MO. Furthermore, …


Three Models Of Anthrax Toxin Effects On The Map-Kinase Pathway And Macrophage Survival, Daniel J. Schneider Mar 2008

Three Models Of Anthrax Toxin Effects On The Map-Kinase Pathway And Macrophage Survival, Daniel J. Schneider

Theses and Dissertations

Lethal factor (LF), a component of anthrax toxin, is the primary virulence factor that allows Bacillus anthracis to evade the immune response by blocking the activation of mitogen-activated protein kinase (MAPK) enzymes. This research modifies three published MAPK models to reflect this signal inhibition and to estimate a first-order reaction rate by fitting the models to published viability data for two macrophage cell lines cultured with the LF-producing Bacillus anthracis-Vollum1B strain. One model appears to be ill-suited for this purpose because not all relevant MAPK components could be integrated into the inhibition equations. Despite different underlying parameters and values, the …


In Vitro Toxicity And Inflammation Response Induced By Copper Nanoparticles In Rat Alveolar Macrophages, Brian M. Clarke Mar 2008

In Vitro Toxicity And Inflammation Response Induced By Copper Nanoparticles In Rat Alveolar Macrophages, Brian M. Clarke

Theses and Dissertations

Nanotechnology is a thriving industry and has the potential to benefit society in numerous ways. However, not all environmental and human health concerns of nanomaterials have been addressed. Thus, the purpose of this research was to investigate the toxicity and inflammation potential (using cytokines TNF-alpha and IL-6 as indicators) of various sized copper nanoparticles (40, 60, and 80 nm) in rat alveolar macrophages. Toxicity measurements were accomplished by means of in vitro techniques and toxicity mechanisms were studied by measuring reactive oxygen species (ROS) production. In addition, cytokine measurements used enzyme-linked immunosorbent assay (ELISA) methods. Results show copper nanoparticles as …


In Vitro Toxicity Of Aluminum Nanoparticles In Rat Alveolar Macrophages, Andrew J. Wagner Mar 2006

In Vitro Toxicity Of Aluminum Nanoparticles In Rat Alveolar Macrophages, Andrew J. Wagner

Theses and Dissertations

Nanomaterials, which are by definition in the 1 - 100 nanometer range, have numerous possible benefits to society, but currently there is a lack of data that characterizes these materials effects on human health and environment. In general nanomaterials are of interest to the Air Force because of their applications in electronics, sensors, munitions and energetic/reactive systems. Nanoparticles such as aluminum have been considered for enhancing propulsion in solid rocket fuel. To date, only a few studies have looked at the toxicological effects of direct exposure to nanoparticles, none with aluminum. It is important to increase the understanding of the …


Comparison Of Leukocyte Classes Most Likely To Cause Vascular Dysfunction In Preeclampsia, Kristen Anne Cadden Jan 2006

Comparison Of Leukocyte Classes Most Likely To Cause Vascular Dysfunction In Preeclampsia, Kristen Anne Cadden

Theses and Dissertations

Leukocytes are activated in women with preeclampsia, but the class of leukocyte most likely to cause vascular dysfunction is not known. We hypothesized that neutrophils may be the class of leukocyte most involved in causing this dysfunction because neutrophils are the most abundant of the leukocytes and their numbers increase during pregnancy. In this study we compared vascular infiltration of neutrophils (CD66b) with monocytes/macrophages (CD14) and lymphocytes (CD99) in normal non-pregnant women (NNP), normal pregnant women (NP), and preeclamptic women (PE). There was no significant difference in the infiltration of lymphocytes into the maternal vasculature in PE as compared to …