Macrophages Electron transport

When induced in macrophages, iNOS produces large amounts of NO which represents a major cytotoxic principle of those cells. Due to its affinity to protein-bound iron, NO can inhibit a number of key enzymes that contain iron in their catalytic centers. These include ribonucleotide reductase (rate-limiting in DNA replication), iron-sulfur cluster-dependent enzymes (complex I and II) involved in mitochondrial electron transport and cis-aconitase in the citric acid cycle. In addition, higher concentrations of NO,... 

Granger, D. L., and Lehninger, A. L. (1982). Sites of inhibition of mitochondrial electron transport in macrophage-injured neoplastic cells. J. Cell Biol. 95, 521-535. 

Wharton, M., Granger, D. L., and Durack, D. T. (1988). Mitochondrial iron loss from leukemia cells injured by macrophages. A possible mechanism for electron transport chain defects. J. Immunol. 141, 1311-1317. 

NO also has cytotoxic effects when synthesized in large quantities, eg, by activated macrophages. For example, NO inhibits metalloproteins involved in cellular respiration, such as the citric acid cycle enzyme aconitase and the electron transport chain protein cytochrome oxidase. Inhibition of the heme-containing cytochrome P450 enzymes by NO is a major pathogenic mechanism in inflammatory liver disease. 

Since other membranes have an integral transmembrane electron transport system, the question arises whether these electron carriers can be involved in an oxidation-reduction driven proton movement. In neutrophil as well as macrophage plasma membranes, the answer is already yes. The superoxide-producing NADPH oxidase in these membranes is associated with a channel for proton movement to accompany the electron flow when internal NADPH is oxidized by external oxygen to produce superoxide (Nanda et al., 1993). This is a relatively simple electron transport system which contains a heterodimeric cytochrome b which also binds flavin. Thus, two proteins in a transmembrane electron transport system can transfer protons across the membrane. 

NADH oxidation, and electron transport (Nriagu 1980). Cadmium is a potent enzyme inhibitor, affecting a variety of plant enzymes such as PEP carboxylase, lipase, invertase (Yu 1997), and others. Extensive reports are available concerning Cd-dependent inhibition of enzymes from animals and humans. Alkaline phosphatase and ATPases of myosin and pulmonary alveolar macrophage cells are examples. 

Enzyme-catalyzed reactions Electron transport in mitochondria Signal transduction and gene expression Activation of nuclear transcription factors Oxidative damage to molecules, cells, and tissues Antimicrobial action of neutrophils and macrophages Aging and disease... 

Taya A, Hotz G, Seidel A. 1986. Biochemical and electron microscopic studies on binding and transport of americium and plutonium hydroxide polymers in bovine alveolar macrophages and rat lungs. J Aerosol Sci 17(3) 370-375. 

Figure 2 (A) SEM of an ADB 48 hours after exposure to chrysotile asbestos fibers. Many of the deposited fibers have been covered by the alveolar epithebum (arrows) and others have been phagocytized by AM. (B) Transmission electron micrograph of chrysotile asbestos fibers (arrow heads) that have been transported fiom the alveolar space ( ), through the AE, and are about to he deposited in the underlying alveolar interstitium. An interstitial MC and adjacent extracellular collagen (Q are observed. Abbreviations SEM, scanning electron micrograph ADB, alveolar duct bifurcations AM, alveolar macrophages AE, alveolar epithelium MC, mesenchymal cell.

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