Thesis (M.P.H.)--University of Michigan, 1947.

Thesis (Ph. D.)--Ohio State University, 2009. / Title from first page of PDF file. Includes bibliographical references (p. 135-150).

Thesis (M.P.H.)--University of Michigan, 1947.

Thesis (Ph.D.)--University of Melbourne, Dept. of Paediatrics, 2010. / Typescript. Includes bibliographical references (p: 237-258)

Thesis (Ph.D.) - University of Queensland, 2005. / Includes bibliography.

Thesis (Ph.D.)--University of California, San Francisco, 2004. / Includes bibliographical references. Also available online.

Thesis (Ph. D.)--Ohio State University, 2005. / Available online via OhioLINK's ETD Center; full text release delayed at author's request until 2008 Nov 30

D.Litt. et Phil. (Psychology) / Please refer to dull text to view abstract

M. Tech. / The persistent presence of neutrophils is associated with a wide range of inflammatory diseases. Resolution of inflammation in these diseases is also associated with the ingestion of apoptotic neutrophils by macrophages. Inflammation and apoptosis of inflammatory cells are common known features observed in the lung following exposure to crystalline silica. What is not known is how well these apoptotic cells are cleared by macrophages in the presence of crystalline silica? To investigate the latter, we incubated the U937 macrophages and neutrophils with crystalline silica and found that it could increase their apoptosis and necrosis especially those of the U937 cells. We then examined the ability of crystalline silica to induce the production of cytokines (TNF-α, IFN-γ and IL-1β) as well as NO by these cells. We found that these particles could increase the production of TNF-α, IL-1β and NO but not IFN-γ in a time-and concentration-dependent manner. We also assessed the ability of crystalline silica to alter the levels of GSH in neutrophils and U937 macrophages. We found that it could drastically decrease the levels of this antioxidant in U937 macrophages with no additional effect in neutrophils as these latter cells would have low levels of GSH prior to their incubation with crystalline silica. Finally, we examined the effect of crystalline silica on the ability of U937 macrophages to phagocytose apoptotic neutrophils. We found that while untreated U937 macrophages were able to phagocytose apoptotic neutrophils, the presence of crystalline silica reduced this ability by 15%. Taken together, our results suggest that exposure to crystalline silica impairs the clearance of apoptotic neutrophils by decreasing their phagocytosis by macrophages and thus prevents the resolution of inflammation.

Previous studies with conjugates containing the NH2-terminal and COOH-terminal antigenic determinants of oxidized ferredoxin from C. pasteurianum indicated a need for at least two determinants to stimulate DNA synthesis in sensitized lymphocytes. This suggested a mechanism involving cell cooperation, a possibility which has been investigated here by selectively inactivating cells binding one or the other of the determinants. Cells from immunized guinea pigs were tested in vitro for their capacity to bind antigen or to be stimulated by it before and after "antigen suicide" with radioiodinated conjugates containing the NH2-terminal or COOH-terminal determinants of oxidized ferredoxin. A microculture system for assessing antigen induced stimulation of 3H-thymidine uptake by lymphocytes was developed for this work. The data show that: 1) Lymphocytes from unimmunized guinea pigs bind both NH2-terminal and COOH-terminal determinants at a frequency of about 10-4. In immune animals the proportion of antigen binding cells increased about 4-6 fold. The frequency of cells binding the determinants depends markedly on the specific activity of antigens employed. 2) Both T and B lymphocytes bind the antigenic determinants from oxidized ferredoxin. 3) Specific inactivation of cells binding either determinant was achieved by antigen suicide with ¹²⁵I-NH₂-terminal or ¹²⁵I COOH-terminal s-BSA conjugates. Synergy occurs between the NH2-terminal binding cells and COOH-terminal binding cells in the proliferative response of sensitized lymph node cells challenged with oxidized ferredoxin in vitro. Evidence from B cell depletion studies indicates that this is a T cell-T cell interaction. / Science, Faculty of / Microbiology and Immunology, Department of / Graduate