AI Article Synopsis

  • * ROS disrupt cellular activities and lead to increased inflammation by activating immune cells, which produce pro-inflammatory cytokines that worsen tissue damage, especially in the vascular system.
  • * Macrophages, key players in the inflammatory response, generate ROS mainly through the enzyme NADPH oxidase, which is crucial for host defense but can also trigger harmful signaling in surrounding cells.

Article Abstract

Oxidative stress has been implicated in a number of pathologic conditions including ischemia/reperfusion damage and sepsis. The concept of oxidative stress refers to the aberrant formation of ROS (reactive oxygen species), which include O(2)(•-), H(2)O(2), and hydroxyl radicals. Reactive oxygen species influences a multitude of cellular processes including signal transduction, cell proliferation and cell death. ROS have the potential to damage vascular and organ cells directly, and can initiate secondary chemical reactions and genetic alterations that ultimately result in an amplification of the initial ROS-mediated tissue damage. A key component of the amplification cascade that exacerbates irreversible tissue damage is the recruitment and activation of circulating inflammatory cells. During inflammation, inflammatory cells produce cytokines such as tumor necrosis factor-α (TNFα) and IL-1 that activate endothelial cells (EC) and epithelial cells and further augment the inflammatory response. Vascular endothelial dysfunction is an established feature of acute inflammation. Macrophages contribute to endothelial dysfunction during inflammation by mechanisms that remain unclear. Activation of macrophages results in the extracellular release of O(2)(•-) and various pro-inflammatory cytokines, which triggers pathologic signaling in adjacent cells. NADPH oxidases are the major and primary source of ROS in most of the cell types. Recently, it is shown by us and others that ROS produced by NADPH oxidases induce the mitochondrial ROS production during many pathophysiological conditions. Hence measuring the mitochondrial ROS production is equally important in addition to measuring cytosolic ROS. Macrophages produce ROS by the flavoprotein enzyme NADPH oxidase which plays a primary role in inflammation. Once activated, phagocytic NADPH oxidase produces copious amounts of O(2)(•-) that are important in the host defense mechanism. Although paracrine-derived O(2)(•-) plays an important role in the pathogenesis of vascular diseases, visualization of paracrine ROS-induced intracellular signaling including Ca(2+) mobilization is still hypothesis. We have developed a model in which activated macrophages are used as a source of O(2)(•-) to transduce a signal to adjacent endothelial cells. Using this model we demonstrate that macrophage-derived O(2)(•-) lead to calcium signaling in adjacent endothelial cells.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3369665PMC
http://dx.doi.org/10.3791/3511DOI Listing

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