The expanding role of NADPH oxidases in health and disease: no longer just agents of death and destruction

Quinn, Mark T.; Ammons, Mary Cloud B.; DeLeo, Frank R.

doi:10.1042/cs20060059

Cited by 152 publications

(136 citation statements)

References 236 publications

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“…In these studies, we observed strong differences in basal expression of numerous genes when comparing C57BL/6 and gp91 phoxϪ/Ϫ mice, even before exposure to conidia. These differences could be due in part to compensatory responses in gp91 phoxϪ/Ϫ mice, which lack metabolic regulatory mechanisms contributed by NADPH oxidase activity (41). In support of this hypothesis, differences in constitutive gene transcription have also been found in PMN from human patients with Xlinked chronic granulomatous disease compared with normal individuals (42).…”

Section: Discussionsupporting

confidence: 66%

Reduced Nicotinamide Adenine Dinucleotide Phosphate Oxidase-Independent Resistance to Aspergillus fumigatus in Alveolar Macrophages

Cornish

Hurtgen

McInnerney

et al. 2008

The Journal of Immunology

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The fungal pathogen Aspergillus fumigatus is responsible for increasing numbers of fatal infections in immune-compromised humans. Alveolar macrophages (AM) are important in the innate defense against aspergillosis, but little is known about their molecular responses to fungal conidia in vivo. We examined transcriptional changes and superoxide release by AM from C57BL/6 and gp91phox−/− mice in response to conidia. Following introduction of conidia into the lung, microarray analysis of AM showed the transcripts most strongly up-regulated in vivo to encode chemokines and additional genes that play a critical role in neutrophil and monocyte recruitment, indicating that activation of phagocytes represents a critical early response of AM to fungal conidia. Of the 73 AM genes showing ≥2-fold changes, 8 were also increased in gp91phox−/− mice by conidia and in C57BL/6 mice by polystyrene beads, suggesting a common innate response to particulate matter. Ingenuity analysis of the microarray data from C57BL/6 mice revealed immune cell signaling and gene expression as primary mechanisms of this response. Despite the well-established importance of phagocyte NADPH oxidase in resisting aspergillosis, we found no evidence of this mechanism in AM following introduction of conidia into the mouse lung using transcriptional, luminometry, or NBT staining analysis. In support of these findings, we observed that AM from C57BL/6 and gp91phox−/− mice inhibit conidial germination equally in vitro. Our results indicate that early transcription in mouse AM exposed to conidia in vivo targets neutrophil recruitment, and that NADPH oxidase-independent mechanisms in AM contribute to inhibition of conidial germination.

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Section: Discussionsupporting

confidence: 66%

Reduced Nicotinamide Adenine Dinucleotide Phosphate Oxidase-Independent Resistance to Aspergillus fumigatus in Alveolar Macrophages

Cornish

Hurtgen

McInnerney

et al. 2008

The Journal of Immunology

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“…Fraction T-I and T-II exhibited the most potent immunoenhancing activity and stimulated murine J774.A1 macrophages to produce significant levels of NO and ROS. Both NO and ROS play important roles in a variety of physiological processes and are key participants in host defense (reviewed by [36,37]). In addition, these reactive oxidants have also been shown to be involved in the regulation of apoptosis and immune homeostasis [38].…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory activity of acidic polysaccharides isolated from Tanacetum vulgare L.

Xie

Schepetkin

Quinn

2007

International Immunopharmacology

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Tanacetum vulgare L. (Tansy) has been extensively used in folk medicine for treatment of a variety of medical disorders. In the present study, we isolated and purified four acidic polysaccharide fractions (designated T-I to T-IV) from Tansy florets by the sequential use of hot-water extraction, ethanol precipitation, ultra-filtration, anion-exchange, and size-exclusion chromatography. The average M r of fractions T-I through T-IV was estimated to be 326, 151, 64 and 9 kDa, respectively, as determined by high performance size-exclusion chromatography analysis. Sugar composition analysis revealed that Tansy polysaccharides consisted primarily of galacturonic acid, galactose, arabinose, and rhamnose. Fractions T-II through T-IV contained an arabinogalactan type II structure, as determined by reaction with Yariv reagent. High M r fractions T-I and T-II exhibited potent macrophage/monocyte-activating activity, enhancing production of reactive oxygen species (ROS), nitric oxide (NO), and tumor necrosis factor α (TNF-α) by J774.A1 murine macrophages, and activating nuclear factor κB (NF-κB) in THP-1 human monocytes. In addition, Tansy polysaccharides stimulated human neutrophil function by greatly enhancing neutrophil myeloperoxidase (MPO) release. Furthermore, the low M r fraction T-IV had potent complementfixing activity, which may also contribute to the anti-inflammatory and would-healing properties of Tansy extracts. Taken together, our results provide a molecular basis to explain at least part of the beneficial therapeutic effects of Tansy extracts, and support the concept of using Tansy polysaccharides as an immunotherapeutic adjuvant.

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“…With a turnover of 8.5 years in adults (Coclet et al, 1989), thyrocytes have time to accumulate H 2 O 2 -induced DNA damages. Hydrogen peroxide has been found to play a role in several human cancers (Quinn et al, 2006). Thus, a number of arguments support a role of H 2 O 2 in the initiation of PTC, and in particular in patients not exposed to radiation.…”

mentioning

confidence: 99%

Genome-wide gene expression profiling suggests distinct radiation susceptibilities in sporadic and post-Chernobyl papillary thyroid cancers

et al. 2007

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Papillary thyroid cancers (PTCs) incidence dramatically increased in the vicinity of Chernobyl. The cancer-initiating role of radiation elsewhere is debated. Therefore, we searched for a signature distinguishing radio-induced from sporadic cancers. Using microarrays, we compared the expression profiles of PTCs from the Chernobyl Tissue Bank (CTB, n ¼ 12) and from French patients with no history of exposure to ionising radiations (n ¼ 14). We also compared the transcriptional responses of human lymphocytes to the presumed aetiological agents initiating these tumours, g-radiation and H 2 O 2 . On a global scale, the transcriptomes of CTB and French tumours are indistinguishable, and the transcriptional responses to g-radiation and H 2 O 2 are similar. On a finer scale, a 118 genes signature discriminated the g-radiation and H 2 O 2 responses. This signature could be used to classify the tumours as CTB or French with an error of 15 -27%. Similar results were obtained with an independent signature of 13 genes involved in homologous recombination. Although sporadic and radio-induced PTCs represent the same disease, they are distinguishable with molecular signatures reflecting specific responses to g-radiation and H 2 O 2 . These signatures in PTCs could reflect the susceptibility profiles of the patients, suggesting the feasibility of a radiation susceptibility test.

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The expanding role of NADPH oxidases in health and disease: no longer just agents of death and destruction

Cited by 152 publications

References 236 publications

Reduced Nicotinamide Adenine Dinucleotide Phosphate Oxidase-Independent Resistance to Aspergillus fumigatus in Alveolar Macrophages

Reduced Nicotinamide Adenine Dinucleotide Phosphate Oxidase-Independent Resistance to Aspergillus fumigatus in Alveolar Macrophages

Immunomodulatory activity of acidic polysaccharides isolated from Tanacetum vulgare L.

Genome-wide gene expression profiling suggests distinct radiation susceptibilities in sporadic and post-Chernobyl papillary thyroid cancers

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