Characterization of hydrogen peroxide production by Duox in bronchial epithelial cells exposed to Pseudomonas aeruginosa

National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda 20852, USA.
FEBS letters (Impact Factor: 3.17). 03/2010; 584(5):917-22. DOI: 10.1016/j.febslet.2010.01.025
Source: PubMed

ABSTRACT Hydrogen peroxide production by the NADPH oxidase Duox1 occurs during activation of respiratory epithelial cells stimulated by purified bacterial ligands, such as lipopolysaccharide. Here, we characterize Duox activation using intact bacterial cells of several airway pathogens. We found that only Pseudomonas aeruginosa, not Burkholderia cepacia or Staphylococcus aureus, triggers H2O2 production in bronchial epithelial cells in a calcium-dependent but predominantly ATP-independent manner. Moreover, by comparing mutant Pseudomonas strains, we identify several virulence factors that participate in Duox activation, including the type-three secretion system. These data provide insight on Duox activation by mechanisms unique to P. aeruginosa.

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Available from: Balazs Rada, Sep 29, 2015
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    • "Epithelial lung cells exposed to particulate matter will upregulate ROS in an attempt to protect the cells against a foreign substance. Hydrogen peroxide release within epithelial lung cells is a non-specific defense mechanism designed primarily to kill pathogens [48], but the response is also triggered when cells encounter particulate matter [49]. Hence, the formation of ROS in cell-free aqueous systems is not a prerequisite for the upregulation of ROS when particles are added to lung cells, but particle-driven ROS formation may lead to enhanced ROS upregulation. "
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    Geochemical Transactions 04/2012; 13(1):4. DOI:10.1186/1467-4866-13-4 · 1.62 Impact Factor
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    • "Dual oxidases (Duox) are also expressed by epithelial cells in the airways and produce hydrogen peroxide, which contributes to antimicrobial activities through the lactoperoxidase system (Geiszt et al., 2003). This theoretically allows for partial reconstitution of ROS production in the lung in response to bacterial infection, but interesting it has been shown that Bcc does not stimulate hydrogen peroxide production by bronchial epithelial cells through Duox (Rada and Leto, 2010). "
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    ABSTRACT: The Burkholderia cepacia complex (Bcc) is a group of Gram-negative bacteria that are ubiquitous in the environment and have emerged as opportunistic pathogens in immunocompromised patients. The primary patient populations infected with Bcc include individuals with cystic fibrosis (CF), as well as those with chronic granulomatous disease (CGD). While Bcc infection in CF is better characterized than in CGD, these two genetic diseases are not obviously similar and it is currently unknown if there is any commonality in host immune defects that is responsible for the susceptibility to Bcc. CF is caused by mutations in the CF transmembrane conductance regulator, resulting in manifestations in various organ systems, however the major cause of morbidity and mortality is currently due to bacterial respiratory infections. CGD, on the other hand, is a genetic disorder that is caused by defects in phagocyte NADPH oxidase. Because of the defect in CGD, phagocytes in these patients are unable to produce reactive oxygen species, which results in increased susceptibility to bacterial and fungal infections. Despite this significant defect in microbial clearance, the spectrum of pathogens frequently implicated in infections in CGD is relatively narrow and includes some bacterial species that are considered almost pathognomonic for this disorder. Very little is known about the cause of the specific susceptibility to Bcc over other potential pathogens more prevalent in the environment, and a better understanding of specific mechanisms required for bacterial virulence has become a high priority. This review will summarize both the current knowledge and future directions related to Bcc virulence in immunocompromised individuals with a focus on the roles of bacterial factors and neutrophil defects in pathogenesis.
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