Antioxidant macromolecules in the epithelial lining fluid of the normal human lower respiratory tract.

Cantin, André M.; Fells, G A; Hubbard, Richard C.; Crystal, Ronald G.

doi:10.1172/jci114798

Cited by 124 publications

(77 citation statements)

References 52 publications

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“…It has generally been accepted that catalase provides little protection against extracellular H202 because the enzyme is predominantly located in peroxisomes (7,10) and is thought not to be secreted (29). Nevertheless, the present findings with CEM cells when coupled with the reported secretion of thioredoxin by human T-lymphotropic virus I-infected T cells (28) damage than other lymphoid cells, a feature that may be crucial for their ability to survive and function in close proximity to activated macrophages and neutrophils at sites of chronic inflammation (30).…”

Section: Discussionmentioning

confidence: 99%

Autocrine production of extracellular catalase prevents apoptosis of the human CEM T-cell line in serum-free medium.

Sandstrom

Buttke

1993

Proc. Natl. Acad. Sci. U.S.A.

168

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CCRF-CEM is a human T-cell line originally isolated from a child with acute lymphoblastic leukemia. At cell densities > 2 x 10 cells per ml, CEM cells grow in serum-free medium, but at lower cell densities the cultures rapidly undergo apoptosis, or programmed cell death. The viability of lowdensity CEM cells could be preserved by supplementing the serum-free medium with "conditioned" medium from highdensity CEM cultures, but a variety of known growth factors and lymphokines were ineffective. Fractionation ofconditioned medium by sequential chromatography on DEAE-cellulose, propyl agarose, chromatofocusing, and hydrophobic-interaction HPLC resulted in the isolation of a 60-kDa protein capable ofsustaining CEM growth in the absence ofserum. The active protein was identified as human catalase based on its amino acid sequence and composition and was subsequently shown to exhibit catalase activity and to be replaceable by human erythrocyte catalase or bovine liver catalase. Comparison of the level of intracellular catalase activity with the amount released into the culture medium demonstrated that the latter accounted for <3% of the total catalase activity present in the cell culture. These findings show that, despite its low amount, the catalase released by CEM cells, and perhaps by T cells in general, provides a critical rust Ilne of defense against hydrogen peroxide (11202) present in the extracellular milieu.Survival in aerobic conditions has required that organisms develop elaborate antioxidant defense systems to cope with potentially toxic reactive oxygen species (ROS) (1). For example, hydrogen peroxide (H202) is generated from numerous endogenous and exogenous sources including mitochondrial respiration, UV radiation, peroxigenic bacteria, and, in the immune system, from the combined actions of the NADPH oxidase and superoxide dismutase systems of phagocytes (1, 2). It has recently become apparent that ROS can have divergent effects on mammalian cell growth. In some cases low doses of H202 induced cells to undergo apoptosis, or programmed cell death (3), whereas in other cases H202 was found to promote cell proliferation (4-7). Such findings suggest that ROS may function as intracellular second messengers (8) and that growth stimulation may occur when cells are protected against excessive ROS toxicity (7).Both prokaryotes and eukaryotes produce catalase, an enzymatic antioxidant that effilciently breaks down H202 into H20 and 02. However, the extensive involvement of the glutathione peroxidase system for intracellular H202 detoxification in cells of higher organisms (9), coupled with the tenet that catalase activity is restricted to peroxisomes (7), raises the question as to what role extraperoxisomal catalase plays in antioxidant defense (10). We report here that CCRF-CEM, an acute T-lymphocytic leukemia cell line (11), displays density-dependent growth characteristics in response to cell-derived extracellular catalase and rapidly undergoes apoptosis when cultured below a critical cell density. Thes...

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Section: Discussionmentioning

confidence: 99%

Autocrine production of extracellular catalase prevents apoptosis of the human CEM T-cell line in serum-free medium.

Sandstrom

Buttke

1993

Proc. Natl. Acad. Sci. U.S.A.

168

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“…The major antioxidants in respiratory tract lining fluid include mucin, reduced glutathione, uric acid, protein (largely albumin), and ascorbic acid (74). There is limited information about respiratory epithelial antioxidant defenses in smokers, and even less about those in patients with COPD.…”

Section: Role Of Oxidants and Antioxidants In Smoking-induced Copdmentioning

confidence: 99%

Pathogenesis of Chronic Obstructive Pulmonary Disease

MacNee¹

2005

Proceedings of the American Thoracic Society

361

220

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The current paradigm for the pathogenesis of chronic obstructive pulmonary disease is that chronic airflow limitation results from an abnormal inflammatory response to inhaled particles and gases in the lung. Airspace inflammation appears to be different in susceptible smokers and involves a predominance of CD8 ؉ T lymphocytes, neutrophils, and macrophages. Studies have characterized inflammation in the peripheral airspaces in different stages of disease severity. Two other processes have received considerable research attention. The first is a protease-antiprotease imbalance, which has been linked to the pathogenesis of emphysema. However, the hypothesis of an increased protease burden associated with functional inhibition of antiproteases has been difficult to prove and is now considered an oversimplification. The second process, oxidative stress, has a role in many of the pathogenic processes of chronic obstructive pulmonary disease and may be one mechanism that enhances the inflammatory response. In addition, it has been proposed that the development of emphysema may involve alveolar cell loss through apoptosis. This mechanism may involve the vascular endothelial growth factor pathway and oxidative stress.Keywords: apoptosis; emphysema; inflammation; oxidative stress; protease-antiprotease imbalance Chronic obstructive pulmonary disease (COPD) is a slowly progressive condition characterized by airflow limitation, which is largely irreversible (1). Cigarette smoking is the main etiologic factor in this condition, far outweighing any of the other risk factors. The pathogenesis of COPD is therefore strongly linked to the effects of cigarette smoke on the lungs. There is a general relationship between the extent of the smoking history and the severity of the airflow limitation; however, there is a huge individual variation. Fletcher and Peto (2), in an 8-yr prospective study of working men in West London, showed that the average decline in FEV 1 in smokers is faster (60 ml/yr) than in nonsmokers (30 ml/yr). However, smokers who develop COPD have an average decline in FEV 1 of greater than 60 ml/yr, and only 15 to 20% of smokers develop clinically significant COPD. It is from these studies that the concept of the susceptible smoker developed. SUBTYPES OF COPD Chronic BronchitisThe cough and sputum production that define chronic bronchitis result from an innate immune response to inhaled toxic particles and gases in cigarette smoke. In chronic bronchitis there is inflammation in the epithelium of the central airways and in the mucus-producing glands (3). This airway inflammation is associ-

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“…Metalbinding proteins such as lactoferrin, transferrin, and ceruloplasmin also presumably function as intralumenal airway antioxidants. Although most major enzymatic antioxidants are primarily intracellular, superoxide dismutase and small amounts of catalase and glutathione peroxidase (GSHPx) have also been described in airway fluids [37,38].…”

Section: Oxidative Stress In the Lungmentioning

confidence: 99%

Antioxidants in cystic fibrosis☆Conclusions from the CF Antioxidant Workshop, Bethesda, Maryland, November 11-12, 2003

Cantin

White

Cross

et al. 2007

Free Radical Biology and Medicine

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Although great strides are being made in the care of individuals with cystic fibrosis (CF), this condition remains the most common fatal hereditary disease in North America. Numerous links exist between progression of CF lung disease and oxidative stress. The defect in CF is the loss of function of the transmembrane conductance regulator (CFTR) protein; recent evidence that CFTR expression and function are modulated by oxidative stress suggests that the loss may result in a poor adaptive response to oxidants. Pancreatic insufficiency in CF also increases susceptibility to deficiencies in lipophilic antioxidants. Finally the airway infection and inflammatory processes in the CF lung are potential sources of oxidants that can affect normal airway physiology and contribute to the mechanisms causing characteristic changes associated with bronchiectasis and loss of lung function. These multiple abnormalities in the oxidant/antioxidant balance raise several possibilities for therapeutic interventions that must be carefully assessed. IntroductionCystic fibrosis (CF) is the most common fatal disease caused by a single gene defect in Europe and North America [1,2]. The defective gene was identified in 1989 [3][4][5] and shown to encode the cystic fibrosis trans-membrane conductance regulator protein (CFTR). CFTR is a cyclic AMP-regulated anion channel with greatest selectivity for chloride, and bicarbonate [6][7][8]. Furthermore, CFTR regulates sodium transport across epithelial membranes through interactions with the epithelial sodium channel ENaC [9], and facilitates the trans-membrane export of the small organic anionic peptide glutathione [10]. The expression of CFTR is located in the apical membrane of epithelial cells that line mucous membranes and submucosal glands ☆ A list of participants may be found in the Acknowledgments.

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Antioxidant macromolecules in the epithelial lining fluid of the normal human lower respiratory tract.

Cited by 124 publications

References 52 publications

Autocrine production of extracellular catalase prevents apoptosis of the human CEM T-cell line in serum-free medium.

Autocrine production of extracellular catalase prevents apoptosis of the human CEM T-cell line in serum-free medium.

Pathogenesis of Chronic Obstructive Pulmonary Disease

Antioxidants in cystic fibrosis☆Conclusions from the CF Antioxidant Workshop, Bethesda, Maryland, November 11-12, 2003

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