Glutathione release by pulmonary alveolar macrophages in response to particles in vitro

Boehme, D.S.; Maples, Kirk R.; Henderson, Rogene F.

doi:10.1016/0378-4274(92)90046-m

Cited by 36 publications

(18 citation statements)

References 21 publications

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“…Whilst synthesis of GSH is well-characterized [32], little is presently understood about the export of this moiety into RTLF. The action of O 3 on resident airway macrophages in rabbits has been shown to result in increased intracellular GSH concentrations; an increase subsequently transferred to the extracellular compartment [33]. However, whilst this mechanism is consistent with the observed results, the time course occurs over days, and not hours as observed in this study, suggesting that the increase in BW/BAL fluid GSH was more likely to be a function of macrophage death than a regulated adaptive response.…”

Section: Discussionsupporting

confidence: 88%

Personally measured weekly exposure to NO<SUB>2</SUB> and respiratory health among preschool children

Mukala¹,

Pekkanen²,

Tiittanen³

et al. 1999

Eur Respir J

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This study sought to clarify the early events occurring within the airways of healthy human subjects performing moderate intermittent exercise following ozone challenge.Thirteen healthy nonsmoking subjects were exposed in a single blinded, crossover control fashion to 0.2 parts per million (ppm) O 3 and filtered air for 2 h, using a standard intermittent exercise and rest protocol. Lung function was assessed pre-and immediately post-exposure. Bronchoscopy was performed with endobronchial mucosal biopsies, bronchial wash (BW) and bronchoalveolar lavage (BAL) 1.5 h after the end of the exposure period. Respiratory tract lining fluid (RTLF) redox status was assessed by measuring a range of antioxidants and oxidative damage markers in BW and BAL fluid samples.There was a significant upregulation after O 3 exposure in the expression of vascular endothelial P-selectin (p<0.005) and intercellular adhesion molecule-1 (p<0.005). This was associated with a 2-fold increase in submucosal mast cells (p<0.005) in biopsy samples, without evidence of neutrophilic inflammation, and a decrease in BAL fluid macrophage numbers (1.6-fold, p<0.005), with an activation of the remaining macrophage subset (2.5-fold increase in % human leukocyte antigen (HLA)-DR+ cells, p<0.005). In addition, exposure led to a 4.5-fold and 3.1-fold increase of reduced glutathione (GSH) concentrations, in BW and BAL fluid respectively (p<0.05), with alterations in urate and a-tocopherol plasma/RTLF partitioning ratios (p<0.05). Spirometry showed reductions in forced vital capacity (p<0.05) and forced expiratory volume in one second (p<0.01), with evidence of small airway narrowing using forced expiratory flow values (p<0.005).Evidence was found of O 3 -induced early adhesion molecule upregulation, increased submucosal mast cell numbers and alterations to the respiratory tract lining fluid redox status. No clear relationship was demonstrable between changes in these early markers and the lung function decrements observed. The results therefore indicate that the initial lung function decrements are not predictive of, or causally related to the O 3 -induced inflammatory events in normal human subjects. Eur Respir J 1999; 13: 1418±1428.

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Section: Discussionsupporting

confidence: 88%

Personally measured weekly exposure to NO<SUB>2</SUB> and respiratory health among preschool children

Mukala¹,

Pekkanen²,

Tiittanen³

et al. 1999

Eur Respir J

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“…Perhaps this represents an adaptive response to the oxidant stress of cigarette smoking or the inflammatory response (52), or perhaps it occurs subsequent to GSH release from inflammatory cells or RTECs that have been injured or shedded. Indeed, it has been demonstrated that toxic particles, such as quartz and asbestos, cause GSH releases from alveolar macrophages (86) and RTEC shedding is known to occur in most forms of lung inflammation including asthma (87).…”

Section: Comments About Specific Antioxidant Substances In Rtlfsmentioning

confidence: 99%

Oxidants, antioxidants, and respiratory tract lining fluids.

Cross

Vliet

O’Neill

et al. 1994

Environ Health Perspect

222

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Respiratory tract lining fluids (RTLFs) are a heterogeneous group of substances covering the respiratory tract epithelial cells (RTECs) from nasal mucosa to alveoli. Antioxidants contained in the RTLFs can be expected to provide an initial defense against inhaled environmental toxins. The major antioxidants in RTLF include mucin, uric acid, protein (largely albumin), ascorbic acid, and reduced glutathione (GSH). RTLF antioxidants can be augmented by such processes as transudation/exudation of plasma constituents; RTEC secretory processes, including glandular mucus secretion; and cellular antioxidants derived from lysis of RTECs and of inflammatory cells. The antioxidant composition of RTLFs and their role in modulating normal and pathophysiologic RTEC functions under conditions of oxidative stress are yet to be fully characterized. -Environ Health Perspect 102(Suppl 10): 185-191 (1994)

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“…Exposure of C10 cells to asbestos initially causes a decrease in reduced glutathione levels, which later increase at 24 and 48 hours, corresponding to peaks of increased ␥-glutamylcysteine synthetase protein levels. Although not much is known about maintenance of intracellular pools of glutathione, the release of glutathione has been documented from rat alveolar macrophages after exposure in vitro to toxic particulates, such as silica and asbestos (23). A report by Brown et al (24) also shows that fibers can deplete both GSH and ascorbate from lung lining fluid.…”

Section: Discussionmentioning

confidence: 90%

“…Experiments were conducted in accordance with the NIH Guide for the Care and Use of Laboratory Animals (publication 85- 23,1985) following protocols approved by the University of Vermont (Institutional Animal Care and Use Committee). C57/BL6 mice (8 to 12 weeks of age) were exposed to ambient air or chrysotile asbestos (7 mg/m 3 air, 6 hours/day, 5 days/week for 9 days) as described previously (17).…”

Section: Methodsmentioning

confidence: 99%

The γ-Glutamylcysteine Synthetase and Glutathione Regulate Asbestos-induced Expression of Activator Protein-1 Family Members and Activity

Shukla¹,

Flanders²,

Lounsbury

et al. 2004

Cancer Research

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Asbestos fibers cause persistent increases in activator protein-1 (AP-1) family member proto-oncogenes in lung epithelial and mesothelial cells that are linked to proliferation and cell transformation. Using lung epithelial cells, the progenitor cells of lung cancers, we report that crocidolite asbestos initially depletes intracellular glutathione followed by up-regulation of both catalytic and modifier subunits of ␥-glutamylcysteine synthetase. In vivo asbestos inhalation experiments confirm increased protein levels of ␥-glutamylcysteine synthetase in mouse lungs. We also show that asbestos-induced mRNA levels of fos/jun proto-oncogenes, fra-1 transactivation, and AP-1 to DNA binding activity are glutathione-dependent. Epidermal growth factor receptor activity by asbestos is blocked by N-acetyl-L-cysteine, suggesting that it is an initial redox-activated event leading to downstream AP-1 proto-oncogene up-regulation. The overexpression of subunits of ␥-glutamylcysteine synthetase in combination completely blocked asbestos-induced up-regulation of AP-1 proto-oncogene expression. However, when overexpressed individually, the modifier subunit had more dramatic effects than the catalytic subunit. Our work shows that the glutathione-controlled redox status of the epithelial cell plays a pivotal role in asbestos-induced epidermal growth factor receptor and proto-oncogene activation as well as AP-1 activity.

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Glutathione release by pulmonary alveolar macrophages in response to particles in vitro

Cited by 36 publications

References 21 publications

Personally measured weekly exposure to NO<SUB>2</SUB> and respiratory health among preschool children

Personally measured weekly exposure to NO<SUB>2</SUB> and respiratory health among preschool children

Oxidants, antioxidants, and respiratory tract lining fluids.

The γ-Glutamylcysteine Synthetase and Glutathione Regulate Asbestos-induced Expression of Activator Protein-1 Family Members and Activity

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