Reduced Superoxide Dismutase in Lung Cells of Patients with Asthma

Smith, Lewis J.; Shamsuddin, Mir; Sporn, Peter H. S.; Denenberg, Michael; Anderson, James A.

doi:10.1016/s0891-5849(96)00550-3

Cited by 150 publications

(114 citation statements)

References 41 publications

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“…17,18 The loss of SOD activity likely reflects the increased oxidative and nitrative stress in the asthmatic airway, and may serve as a marker of asthma severity. In support of SOD as a surrogate marker of oxidant stress and asthma severity, Smith and colleagues 18 showed a correlation between the degree of airway reactivity to methacholine and SOD activity levels. Here, reactivity measured as the change in FEV 1 after bronchodilator confirms the association of airway hyperreactivity to SOD activity.…”

Section: Discussionmentioning

confidence: 99%

“…18 On the basis that reduction of SOD activity is directly linked to apoptotic death of bronchial epithelial cells, we hypothesized that diminished SOD activity might be related to physiological parameters of asthma in vivo. To test this, we evaluated airway activity of antioxidant enzymes in nine asthmatics in relation to airflow and responsiveness to inhaled bronchodilator.…”

Section: Relation Of Sod To Clinical Features Of Asthmamentioning

confidence: 99%

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Superoxide Dismutase Inactivation in Pathophysiology of Asthmatic Airway Remodeling and Reactivity

Comhair

Ghosh

et al. 2005

The American Journal of Pathology

175

149

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Airway hyperresponsiveness and remodeling are defining features of asthma. We hypothesized that impaired superoxide dismutase (SOD) antioxidant defense is a primary event in the pathophysiology of hyperresponsiveness and remodeling that induces apoptosis and shedding of airway epithelial cells. Mechanisms leading to apoptosis were studied in vivo and in vitro. Asthmatic lungs had increased apoptotic epithelial cells compared to controls as determined by terminal dUTP nick-end labeling-positive cells. Apoptosis was confirmed by the finding that caspase-9 and -3 and poly (ADP-ribose) polymerase were cleaved. On the basis that SOD inactivation triggers cell death and low SOD levels occur in asthma, we tested whether SOD inactivation plays a role in airway epithelial cell death. SOD inhibition increased cell death and cleavage/activation of caspases in bronchial epithelial cells in vitro. Asthma is commonly diagnosed using physiological measures, but alterations in airway structure are the defining features of asthma. Damage to airway epithelium, eosinophil infiltration, smooth muscle hyperplasia, thickening and aberrant collagen, and protein composition of the basement membrane are well established elements of the asthmatic airway. 1,2 The injury to the bronchial epithelium in asthma is marked by loss of columnar epithelial cells. Extensive loss of cells and denuded basement membrane with few basal cells remaining on the airway surface are noted in severe asthma, but shedding of airway epithelium is present even in clinically mild asthma. 2,3 Physical loss of epithelial lining cells is considered one proximate cause of the airway hyperresponsiveness to inhaled mediators, and has been speculated to contribute to asthmatic airway remodeling, in particular abnormal collagen synthesis. Evidence from organ culture systems supports the concept of an epithelial-mesenchymal unit in which loss of epithelium leads to mucosal myofibroblast and fibroblast proliferation, and collagen deposition. 2,4 -6 Thus, if the epithelial injury and loss could be understood and prevented in asthma, the clinical symptoms of airway hyperresponsiveness and long-term progressive sequelae in the airways, which contribute to fixed airflow limitation, might be prevented.Several reports have proposed that loss of epithelial cells is because of apoptosis based on immunostaining for the proteins that regulate apoptosis, or by detection of DNA strand breaks by immunostaining with the terminal dUTP nick-end labeling (TUNEL) assay. 7-11 However, not all reports have confirmed increased TUNEL positivity in airways. 9 Furthermore, if airway epithelial cells are undergoing increased cell death, it is unclear whether this is because of an inherent cell defect or a response to the asthmatic airway environment. Although nonspecific events related to increased levels of reactive oxygen and

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Section: Discussionmentioning

confidence: 99%

Section: Relation Of Sod To Clinical Features Of Asthmamentioning

confidence: 99%

Superoxide Dismutase Inactivation in Pathophysiology of Asthmatic Airway Remodeling and Reactivity

Comhair

Ghosh

et al. 2005

The American Journal of Pathology

175

149

View full text Add to dashboard Cite

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“…Indeed, chronic states of infl ammation and oxidative stress have been shown to convert HDL from an anti-infl ammatory and anti-atherogenic lipoprotein into a pro-infl ammatory and pro-atherogenic lipoprotein, making it useless for protecting the vessel wall against the effects of atherogenic concentrations of LDL ( 8 ). Asthma also increases infl ammation and oxidative stress (9)(10)(11)(12). Such infl ammatory changes may explain why adult-onset asthma is associated with signifi cant increases in carotid artery intimal-medial thickness in women ( 13 ).…”

Section: Measurements Of Lung Mechanicsmentioning

confidence: 99%

Genetic deletion of apolipoprotein A-I increases airway hyperresponsiveness, inflammation, and collagen deposition in the lung

Wang

Shi

et al. 2010

Journal of Lipid Research

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This article is available online at http://www.jlr.org plays important roles in limiting pulmonary infl ammation and oxidative stress, which if not prevented, will decrease pulmonary artery vasodilatation and increase airway hyperresponsiveness. Although apolipoprotein A-I (apoA-I), the major antiatherogenic apolipoprotein of HDL, is well recognized for protecting the heart against vascular disease, it also protects other vascular beds and organs. Recent studies provide new evidence supporting the notion that HDL plays a protective role in the lung. ABCA1, which interacts with lipid-poor apoA-I, was earlier shown to be essential for maintaining normal lipid composition and architecture of the lung as well as respiratory physiology ( 1 ). More recently, proteomic studies revealed that homozygous Abstract The relationship between high-density lipoprotein and pulmonary function is unclear. To determine mechanistic relationships we investigated the effects of genetic deletion of apolipoprotein A-I (apoA-I) on plasma lipids, paraoxonase (PON1), pro-infl ammatory HDL (p-HDL), vasodilatation, airway hyperresponsiveness and pulmonary oxidative stress, and infl ammation. ApoA-I null ( apoA-IϪ / Ϫ ) mice had reduced total and HDL cholesterol but increased pro-infl ammatory HDL compared with C57BL/6J mice. Although PON1 protein was increased in apoA-I Ϫ / Ϫ mice, PON1 activity was decreased. ApoA-I defi ciency did not alter vasodilatation of facialis arteries, but it did alter relaxation responses of pulmonary arteries. Central airway resistance was unaltered. However, airway resistance mediated by tissue dampening and elastance were increased in apoA-I Ϫ / Ϫ mice, a fi nding also confi rmed by positive endexpiratory pressure (PEEP) studies. Infl ammatory cells, collagen deposition, 3-nitrotyrosine, and 4-hydroxy-2-nonenal were increased in apoA-I Ϫ / Ϫ lungs but not oxidized phospholipids. Colocalization of 4-hydroxy-2-nonenal with transforming growth factor ␤ -1 (TGF ␤ -1 was increased in apoA-I Ϫ / Ϫ lungs. Xanthine oxidase, myeloperoxidase and endothelial nitric oxide synthase were increased in apoA-I Ϫ / Ϫ lungs. Dichlorodihydrofl uorescein-detectable oxidants were increased in bronchoalveolar lavage fl uid (BALF) in apoA-I Ϫ / Ϫ mice. In contrast, BALF nitrite+nitrate levels were decreased in apoA-I Ϫ / Ϫ mice. These data demonstrate that apoA-I

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“…Disorders [19,21,23]. Besides, many authors have also shown an increase of chemiluminescence in children with bronchial asthma [24][25][26][27] and weakening of this phenomenon in children with recurrent respiratory infections [23,28,29]. The aim of this study was the estimation of mRNA TLR4 receptor expression on the surface of neutrophils and on the chosen parameters of oxidative-antioxidative system in the blood of young children with food allergy.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of TLR4 expression and chosen parameters of oxidative-antioxidative balance in young children with food allergy.

Kamer

Kulig²,

Lewkowicz³

et al. 2010

Folia Histochem Cytobiol.

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Abstract:The authors evaluated mRNA TLR4 expression on neutrophils and the chosen parameters of oxidative-antioxidative balance in blood of 35 children with food allergy (17 of them with IgE-dependent allergy and 18 with IgE-independent allergy) and 15 healthy children without any allergy. The age of these children ranged from 1 to 36 months. Children with food allergy in comparison with healthy children were found to have lower mRNA TLR4 expression, higher average value of chemiluminescence (CL) and its increase after stimulation by fMLP, PMA and OZ as well as lower TAS values. Disturbances of oxidative-antioxidative balance were found in children with food allergy. We suggest that natural immunity is involved in the development of food allergy mechanisms. Moreover, chemiluminescence can be used as an additional diagnostic test.

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Reduced Superoxide Dismutase in Lung Cells of Patients with Asthma

Cited by 150 publications

References 41 publications

Superoxide Dismutase Inactivation in Pathophysiology of Asthmatic Airway Remodeling and Reactivity

Superoxide Dismutase Inactivation in Pathophysiology of Asthmatic Airway Remodeling and Reactivity

Genetic deletion of apolipoprotein A-I increases airway hyperresponsiveness, inflammation, and collagen deposition in the lung

Evaluation of TLR4 expression and chosen parameters of oxidative-antioxidative balance in young children with food allergy.

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