Interactions of Oxygen Radicals with Airway Epithelium

Abstract

Reactive oxygen species (ROS) have been implicated in the pathogenesis of numerous disease processes. Epithelial cells lining the respiratory airways are uniquely vulnerable regarding potential for oxidative damage due to their potential for exposure to both endogenous (e.g., mitochondrial respiration, phagocytic respiratory burst, cellular oxidases) and exogenous (e.g., air pollutants, xenobiotics, catalase negative organisms) oxidants. Airway epithelial cells use several nonenzymatic and enzymatic antioxidant mechanisms to protect against oxidative insult. Nonenzymatic defenses include certain vitamins and low molecular weight compounds such as thiols. The enzymes superoxide dismutase, catalase, and glutatione peroxidase are major sources of antioxidant protection. Other materials associated with airway epithelium such as mucus, epithelial lining fluid, and even the basement membrane/extracellular matrix may have protective actions as well. When the normal balance between oxidants and antioxidants is upset, oxidant stress ensues and subsequent epithelial cell alterations or damage may be a critical component in the pathogenesis of several respiratory diseases. Oxidant stress may profoundly alter lung physiology including pulmonary function (e.g., forced expiratory volumes, flow rates, and maximal inspiratory capacity), mucociliary activity, and airway reactivity. ROS may induce airway inflammation; the inflammatory process may serve as an additional source of ROS in airways and provoke the pathophysiologic responses described. On a more fundamental level, cellular mechanisms in the pathogenesis of ROS may involve activation of intracellular signaling enzymes including phospholipases and protein kinases stimulating the release of inflammatory lipids and cytokines. Respiratory epithelium may be intimately involved in defense against, and pathophysiologic changes invoked by, ROS. -Environ Health Perspect 1 02(Suppl 1 0): 85-90 (1994)

Streptococcus pneumoniaesecretes hydrogen peroxide leading to DNA damage and apoptosis in lung cells

“…Indeed, antioxidants have been shown to confer positive outcome during pneumococcal meningitis in a rat model (67). Constant secretion of such oxidants by serotypes colonizing the upper respiratory tract (URT) can potentially damage the URT epithelia, destabilizing its normal barrier function [e.g., ciliary velocity and mucus production (68)] and facilitating carriage of S. pneumoniae to become more invasive. Given that certain strains of S. pneumoniae are resistant to H 2 O 2 (69), and that H 2 O 2 increases disease pathogenicity, our data suggest that determining the status of the spxB gene in pneumococcal isolates could prove helpful in guiding the use of antioxidants in disease treatment.…”

The Role of Reactive Oxygen and Nitrogen Species in the Response of Airway Epithelium to Particulates

“…Thus, this observation provides strong evidence that generation of oxidative stress is critical to ROFA-induced cytotoxic injury. Additional studies using buthionine sulfoximine to deplete glutathione in RTE cells before exposure to ROFA confirmed that cellular glutathione is involved in protecting RTE cells from ROFA-induced cytotoxicity (38 (40)(41)(42)(43).…”

Superoxide Flux in Endothelial Cells via the Chloride Channel-3 Mediates Intracellular Signaling

“…18, June 2007mechanisms including rapid dismutation to H 2 O 2 , modification of cell-surface proteins, or release of cytokines secondary to endothelial cell activation, we hypothesize a unique signaling cascade specific to the extracellular presence of this anion. The biological effects of extracellular ROS have been studied primarily by adding exogenous H 2 O 2 to target cells (Wright et al, 1994) or by examining autocrine effects on the ROS-producing cells themselves (Thannickal and Fanburg, 2000). No studies, to our knowledge, have demonstrated a role for paracrine-derived O 2 .Ϫ in triggering intracellular ROS generation in a physiological/pathophysiological relevant context.…”