Thesis (Ph. D.)--Ohio State University, 20043. / Title from first page of PDF file. Document formatted into pages; contains xiv, 115 p.; also includes graphics. Includes abstract and vita. Advisor: Clay B. Marsh, Dept.of Pathology. Includes bibliographical references (p. 102-115).

Thesis (M. Phil.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 80-110).

The fetal-maternal interface is an immunologically privileged site where the semi-allogeneic fetus is protected from the maternal immune system. Macrophage represents the second major type (20-30%) of the decidual leukocyte. It functions as important regulator of pregnancy processes such as fetal tolerance, placental development and onset of labor. Changes in macrophage number and activity have been associated with fetal loss and pregnancy complications, including intrauterine growth restriction and preeclampsia. Glycodelin-A (Gd-A) is an abundant glycoprotein with ubiquitous distribution in the first trimester deciduas. It is suggested to be involved in early placental development by its regulatory activities on various immune cells. In this study, it is hypothesized that Gd-A has regulatory role in monocyte/macrophage functions and differentiation. The first objective examined the role of Gd-A in the biological activities of monocytes and macrophages. Gd-A was found to bind to the monocytic cell lines THP-1 and U937, blood monocytes, granulocyte macrophage colony-stimulating factor (GM-CSF)-differentiated macrophages, phorbol 12-myristate 13-acetate-differentiated macrophage and blood macrophages. Gd-A did not affect the viability, proliferation, cell death and phagocytic activity of monocytes and macrophages. The second objective examined the effect of Gd-A on the cytokine secretion of monocytes and macrophages. Gd-A treatment increased the IL-6 production in monocytes and macrophages. IL-6 was associated with the development and growth of the fetal-placental unit. Gd-A also induced the extracellular signal regulated kinases (ERK) activation. The involvement of ERK in stimulating IL-6 production was confirmed by using pharmacological inhibitors. Monocytes in the blood stream are attracted and residue into the deciduas, which differentiated into macrophage under the influence of various decidual soluble factors. Therefore, the third objective studied the possible involvement of Gd-A on the differentiation of monocytes into macrophages. Co-treatment of Gd-A during the GM-CSF-induced differentiation of monocytes stimulated the indoleamine 2,3-dioxygenase (IDO-1) expression and activity in differentiated macrophages. These differentiated macrophages inhibited the proliferation of autologous peripheral blood mononuclear cell in the co-culture system by G0/G1 cell cycle arrest. IDO-1 is one of the reported decidual macrophage markers. It has been suggested to be involved in establishing the tolerogenic environment during pregnancy through L-tryptophan depletion. The increase in IDO-1 expression may be regulated by PKC signaling pathway. Taken together, this thesis reported a novel role of Gd-A on the monocyte differentiation. The present results enhance our knowledge on the regulation of early placentation in human and may shed light on understanding the pathology of complicated pregnancy due to macrophage dysfunction. / published_or_final_version / Obstetrics and Gynaecology / Master / Master of Philosophy

Chronic obstructive pulmonary disease (COPD) is a progressive disease and characterized by persistent airflow limitation. Pathophysiologically it involves many components, including oxidative stress and inflammation of the airways and lungs. Although the primary cause of COPD is smoking, acute exacerbation due to infections can accelerate disease progression, which is a significant cause of morbidity, mortality and burden on healthcare costs. One-half of all acute exacerbations of COPD are associated with bacterial infection, with non-typeable Hemophilus influenzae being the most common pathogen. Staphylococcus pneumonia, one of the most common Gram-positive bacterial pathogens, is also involved in airway infections, either primary or subsequent to viral diseases. To COPD patients the common respiratory pathogens include Gram-negative and Gram-positive bacterial species. Lipopolysaccharide (LPS), a major component of the outer membrane of all Gram-negative bacteria, which is the predominant inducer of inflammatory responses, has been widely studied. On the other hand, less is known about Gram-positive bacteria, which do not contain LPS but express lipoteichoic acid (LTA) as an important proinflammatory constituent in their cell wall. Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter that plays an important role in regulating pulmonary function and pathogenesis of inflammation. In this study, we hypothesize that the serotoninergic system may be involved in LPS- and LTA-induced inflammation in COPD. Since monocyte recruitment to lung is a key step in COPD, this study aims to investigate the effects of LPS or LTA alone and in combination of 5-HT pretreatment on the release of pro-inflammatory cytokines in undifferentiated (i.e. monocytes) and differentiated THP-1 cells (i.e. macrophages). LPS, LTA or 5-HT alone induced the release of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in both monocytes and macrophages. Our findings also showed that 5-HT pretreatment suppressed the LPS-induced IL-8 and MCP-1 release, suggesting that 5-HT might act as an anti-inflammatory mediator. On the other hand, 5-HT pretreatment enhanced the LTA-induced IL-8 and MCP-1 release, indicating that 5-HT might also act as a pro-inflammatory mediator. These results demonstrate that 5-HT may be involved in the differential modulation of inflammatory processes during Gram-negative or Gram-positive infections in COPD. / published_or_final_version / Medicine / Master / Master of Medical Sciences

published_or_final_version / abstract / toc / Pharmacology / Master / Master of Philosophy

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Thesis (M.Phil.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 80-110) Also available in print.

Thesis (M. Phil.)--University of Hong Kong, 2005. / Title proper from title frame. Also available in printed format.