ETD Collection

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    Comparing changes in gene expression across three myeloid cell lines during monocyte-to-macrophage differentiation
    (2022) Cosser, Duncan Alexander
    Monocytes and macrophages exhibit wide heterogeneity in phenotype and function. Despite this variety, cells from model cell lines are often used in experiments without accounting for these differences. We therefore sought to characterize the gene expression profiles of three model myeloid cell lines as they differentiate from a monocyte-like state to a macrophage-like state in order to identify core pathways across cell lines central to the differentiation process, as well as pathways uniquely involved in differentiation in specific cell lines. Using an RNA-seq analysis pipeline we developed, we examined gene expression in three myeloid cell lines – HL60, U937, and THP-1 – during phorbol 12-myristate 13-acetate (PMA)-induced macrophage differentiation. Using gene expression data from three experiments which induced macrophage differentiation in cells from these cell lines using PMA, we constructed gene expression profiles for the cells before and after PMA treatment. We performed differential gene expression analysis to find the genes that are differentially expressed in differentiation, followed by pathway overrepresentation analysis to identify key pathways involved in this process. We identified 1789 genes which were differentially expressed in all cell lines, as well as 2131 genes marked as differentially expressed only in HL60 cells, 1711 in U937 cells, and 2159 genes uniquely differentially expressed in THP-1 cells. Through subsequent investigation of specific gene clusters, we found that there were conserved pathways involved in the monocyte-to-macrophage transition in all cell lines, particularly those involved in phagocytosis and adherence. All cell lines also downregulated maintenance pathways involved in DNA replication and cell cycle control, a behaviour associated with differentiation. Additionally, we found that there were differences in differentiation between the cell lines: the ribosome and oxidative phosphorylation pathways were strongly down-regulated during the transition in HL60 cells, and multiple different components in the cytokine-cytokine receptor interaction pathway were up- and down-regulated in THP-1 cells. A core gene expression profile is associated with PMA-induced differentiation of myeloid cell lines to a macrophage state. However, differentiation of HL60 and THP-1 cells also induces distinct changes in metabolism and cellular signalling. Our research recommends discretion in cross-comparison between experimental results incorporating gene expression studies of these myeloid cells.
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    Cellular iron metabolism in haemochromatotic macrophages
    (1995) Ickinger, Claudia
    HLA-linked haemochromatosis is the result of an inborn error of metabolism inherited as an autosomal recessive gene, closely linked to the HLA locus on chromosome six. In this condition iron absorption is inappropriately high leading to iron overload. Integral to the pathogenesis of this disorder and in contrast to other causes of iron overload, is the relatively modest accumulation of iron within cells of both the small intestine and the reticuloendothelial system and the excessive deposition of iron in parenchymal cells of the liver and other organs. This observation has led to the suggestion that the primary defect(s) could be present in either the gut, the liver, the reticuloendothelial system or all three. Abnormalities in iron uptake by cells, iron transport through and between cells and iron storage in cells have all been suggested as possible mechanisms responsible for the abnormal absorption and distribution of iron in haemochromatosis. Malfunction of the iron transport protein transferrin or its receptor could be responsible for abnormal distribution and iron loading while an abnormality of ferritin iron storage could explain why some cells appear to be unable to store iron and others are iron overloaded.
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    Interleukin 1 production in health and disease
    (1981) Mitchell, Renee
    Interleukin 1 (IL - 1) is a macrophage factor that exerts control over T cell activation. The experimental work presented in this dissertation consists of studies on IL - 1 production by monocytes which can be used as an in vitro correlate for monocyte function, as well as the effect of IL - 1 on immature T cells, that is, thymocytes. In accomplishing the studies presented in this dissertation, a two stage assay was employed. Firstly IL - 1 containing supernatants were produced by stimulated human peripheral blood adherent cells and secondly, the IL - 1 supernatants were assayed on mouse thymocyctes in which these supernatants caused mitogenesis.
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    Characterization of the surface macrophages of the avian lung with observations on a phagocytic respiratory epithelium.
    (2001) Liliane Nganso, Nganpiep
    Due to paucity of free respiratory macrophages (FRMs), compared with mammals, birds have been alleged to be more susceptible to pulmonary infections and affliction. The goal of this study was to question or validate this speculation. Twenty-two mature healthy chickens, 24 domestic ducks and 20 rats were used in various experiments. After pulmonary lavage, FRMs were stained with trypan blue for cell count and with neutral red and trypan blue to assess cell longevity. The cell dynamics was determined by counts made on serial lavages. The morphological attributes of the FRMs and that of the respiratory “phagocytic epithelium” were quantified stereo logically. The rat had a significantly greater number of macrophages and the surface density of the filopodia of the FRMs was higher than that of the birds. The volume density of the vesicular bodies of the macrophages in the three groups of animals was not significantly different. Putative cell flux onto the respiratory surface was observed in the birds and not in the mammal. The surface area of the “phagocytic epithelium” of the birds was very extensive. Compared with mammals, in general, FRMs are fewer in birds. Despite this, the pulmonary defensive status in birds may not necessarily be compromised: functionally, avian FRMs appear to be more efficient. Moreover, their defense function is complimented particularly by the phagocytic activity of the epithelium immediate to the blood-gas barrier, the most vulnerable site of the lung-air sac system.