ELECTRON-TRANSPORT CHAIN ACTIVITY IN NORMAL AND ACTIVATED RAT MACROPHAGES

The pivotal role played by the macrophage in specific and nonspecific immunity suggests that the physiological status of the macrophage may effect the overall regulation of the host defense system. Many studies have evaluated macrophages as effector cells by examining expression of surface markers, cytokine release, or tumor killing in the presence of challenge to host defenses. In this report, the physiological para meter of mitochondrial respiration in freshly isolated rat macrophages is shown to be regulated upon activation in vivo. Assay conditions fo r the reduction of MTT [3-(4,5-dimethylthiazol-2)-2,5-diphenyltetrazol ium bromide] in rat macrophages were optimized and used to quantitate electron transport chain activity as a measure of mitochondrial respir ation. Corynebacterium parvum administration significantly increased t he activity of the mitochondrial electron transport chain in both peri toneal (120% increase, 0.18 +/- .01 vs 0.40 +/- .03, P < 0.01) and liv er macrophages (143% increase, 0.12 +/- .02 vs 0.30 +/- .06, P < 0.01) as detected by augmented MTT reduction. It is demonstrated further th at MTT reduction is distinct from the respiratory burst activity of ma crophages and supports the mitochondrial localization of intracellular MTT reduction in this cell type. These results demonstrate that elect ron transport chain activity is a physiological indicator of macrophag e activation. (C) 1995 Academic Press, Inc.