The immunological effects of mycolic acids (MA) from Mycobacterium tuberculosis on mouse peritoneal macrophages were studied. MA was solubilbized using various carriers. Phagosome uptake and maturation (into late stage phagolysosomes) were compared using fluorescent markers and the confocal microscope. During assessment on the effects of MA on mouse macrophages, changes in morphology and activation of the macrophages were found. This indicated that the MA was immune reactive towards macrophages. The phenotype of cell that develops after in vivo loading with MA was characterized by using cell surface markers: it was found that MA-Ioaded macrophages developed into foam cells. Cell survival, proliferation and macrophage cytokine production were examined to characterize the foam-like cells. The effect of MA-induced foam-like cells on living Mycobacterium tuberculosis was evaluated and increased bactericidal activity was found. The roles of reactive oxygen and nitrogen intermediates via myeloperoxidase were also examined and a theoretical mechanism for the formation of foam cells proposed. The possible role of myeloperoxidase in activation of macrophages, foam cell formation and killing of Mycobacterium tuberculosis is discussed. It is postulated that a possible relationship might exist between tuberculosis and atherosclerosis that is facilitated by mycolic acids.
Thesis (DPhil (Human Physiology))--University of Pretoria, 2005.