Studying The Nadph Oxidase Enzyme And The Different Mutations Resulting From Macrophage Responses

Abstract

The study aimed at assessing whether different mutations in the subunits of NADPH oxidase (gp91^phox, p22^phox, p40^phox, p47^phox, p67^phox) result in an altered macrophage response to infection.The study also examines the production of important inflammatory cytokines in human macrophages in which the expression of different NADPH oxidase subunits have been mutated. Several methods were employed in this study.  Mutations in the various subunits of the NADPH enzyme may lead to the manifestation of CGD. In this study, we theorise that different mutations in the subunits of NADPH oxidase result in an altered macrophage response to infection. LPS was found to decrease macrophage viability but also cause increased production of TNFa and IL-1b. The build-up of dead macrophages may also contribute to the inflammatory respo[1]nse, characterised by TNFα and IL-1β release from the remaining active cells. PMA; used to differentiate U937 cells into macrophages, becomes cytotoxic to macrophages in a time and dose-dependent fashion. The results of the study add to the body of scientific literature that exists on the structure of the NADPH oxidase and the mutagenic approach devised is designed to further the understanding of how the structure of this important enzyme impacts on the activity of the immune system in general, and macrophages in particular. In the longer term, it is hoped that outcomes from this work may inform future therapeutic intervention strategies to combat chronic granulomatous disease