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.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:uj/uj:6990 |
| Date | 17 November 2010 |
| Creators | Mbatha, Nandi |
| Source Sets | South African National ETD Portal |
| Detected Language | English |
| Type | Thesis |
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