Chronic ethanol ingestion potentiates TNF-α-mediated oxidative stress and apoptosis in rat type II cells

Brown, Lou Ann S.; Harris, Frank L.; Guidot, David M.

doi:10.1152/ajplung.2001.281.2.l377

Cited by 83 publications

(100 citation statements)

References 45 publications

(74 reference statements)

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“…The exact mechanism of this alcohol-related immunosuppressive effect is not clear but we suspect that ethanol may have a direct effect on lung epithelial cells, particularly ATII cells and Clara cells. For example, Brown et al have previously shown that chronic ethanol ingestion potentiates apoptosis of ATII cells in rats (Brown et al, 2001). The results of this experiment suggest that chronic ethanol exposure decreases the bioavailability of glutathione (GSH) to mitochondria of ATII cells.…”

Section: Discussionmentioning

confidence: 68%

Maternal alcohol ingestion reduces surfactant protein A expression by preterm fetal lung epithelia

Lazic¹,

Wyatt²,

Matić³

et al. 2007

Alcohol

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In addition to neurodevelopmental effects, alcohol consumption at high levels during pregnancy is associated with immunomodulation and premature birth. Premature birth, in turn, is associated with increased susceptibility to various infectious agents such as Respiratory Syncytial Virus (RSV). The initial line of pulmonary innate defense includes the mucociliary apparatus, which expels microorganisms trapped within the airway secretions. Surfactant proteins A and D (SP-A and SP-D, respectively) are additional components of pulmonary innate immunity and have an important role in pulmonary defense against inhaled pathogens. The purpose of this study was to determine if chronic alcohol consumption during the third trimester of pregnancy alters the function of the mucociliary apparatus and expression of SP-A and SP-D of fetal lung epithelia. Sixteen, date-mated ewes were assigned to two different groups; an ethanol exposed group in which ewes received ethanol through surgically implanted intra-abomasal cannula during the third trimester of pregnancy, and a control group in which ewes received the equivalent amount of water instead of ethanol. Within these two groups, ewes were further randomly assigned to a full-term group in which the lambs were naturally delivered, and a pre-term group in which the lambs were delivered prematurely via an abdominal incision and uterotomy. Ethanol was administered 5 times a week as a 40% solution at 1gr/kg of body weight. The mean maternal serum alcohol concentration (SAC) measured 6 hr post administration was 16.3 +/− 4.36 mg/dL. Tracheas from 6 full-term lambs were collected to assess ciliary beat frequency (CBF). The lung tissue from all (24) lambs was collected for immunohistochemistry (IHC) analysis of SP-A and SP-D protein production and fluorogenic realtime quantitative polymerase chain reaction analysis (qPCR) of SP-A and SP-D mRNA levels. Exposure to ethanol during pregnancy significantly blocked stimulated increase in CBF though ethanol-mediated desensitization of cAMP-dependant protein kinase (PKA). In addition, pre-term born/ethanol-exposed lambs showed significantly decreased SP-A m-RNA expression when compared to the pre-term born/control group (p=0.004); no significant changes were seen with SP-D. The full-term/ethanol exposed lambs had no significant alterations in mRNA levels, but had significantly less detectable SP-A protein when compared to the full-term/control lambs (p=0.02).Corresponding author: Tatjana Lazic, DVM, MS, 2740 Veterinary Medicine, Department of Veterinary Pathology, Iowa State University, Ames, Iowa 50011-1250, 515-294-6688, FAX 515-294-5423, tlazic@iastate.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process error...

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Section: Discussionmentioning

confidence: 68%

Maternal alcohol ingestion reduces surfactant protein A expression by preterm fetal lung epithelia

Lazic¹,

Wyatt²,

Matić³

et al. 2007

Alcohol

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“…Zinc also plays a role in the regulation of cellular glutathione (29) and protects cell membranes from oxidative damage (30). This is particularly intriguing, as we have published extensively on the role of oxidant stress and glutathione depletion in experimental models of chronic alcohol ingestion and in human subjects with alcohol abuse (5,7,(31)(32)(33)(34). Therefore, alcohol-induced zinc deficiency may play a central role in the oxidant stress and consequent cellular dysfunction that has been shown to characterize the alcoholic lung phenotype.…”

Section: Discussionmentioning

confidence: 99%

Zinc Deficiency Mediates Alcohol-Induced Alveolar Epithelial and Macrophage Dysfunction in Rats

Joshi¹,

Mehta²,

Jabber³

et al. 2009

Am J Respir Cell Mol Biol

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Chronic alcohol abuse impairs both alveolar epithelial and macrophage function, and renders individuals susceptible to acute lung injury, pneumonia, and other serious lung diseases. Zinc deficiency, which is known to impact both epithelial and immune cell functions, is also associated with alcohol abuse. In this study, chronic alcohol ingestion (6 wk) in rats altered expression of key zinc transporters and storage proteins in the small intestine and the lung, and decreased zinc levels in the alveolar compartment. Zinc supplementation of alveolar epithelial monolayers derived from alcohol-fed rats in vitro, or of the diets of alcohol-fed rats in vivo, restored alveolar epithelial barrier function, and these improvements were associated with salutary changes in tight junction protein expression and membrane localization. In parallel, dietary zinc supplementation increased intracellular zinc levels, GM-CSF receptor expression, and bacterial phagocytic capacity in the alveolar macrophages of alcoholfed rats. Together, these studies implicate zinc deficiency as a novel mechanism mediating alcohol-induced alveolar epithelial and macrophage dysfunction. Importantly, these findings argue that dietary supplementation can overcome alcohol-induced zinc deficiency and restore alveolar epithelial and macrophage function, and therefore could be an effective treatment for the susceptible alcoholic lung phenotype.

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“…In a rat model of chronic ethanol ingestion, this altered GSH homeostasis in the ELF (14) resulted in increased susceptibility to sepsis-induced acute lung injury as well as impaired alveolar type II cell function and viability (1,5,12). An important role for GSH availability as a predisposing factor to the development of acute lung injury was demonstrated by the ability of GSH precursors to attenuate injury in the rat model (4,5,14).Since alveolar macrophage are dependent on GSH in the ELF, and chronic alcohol decreases this GSH pool, we hypothesized that alcohol-induced macrophage dysfunction was secondary to alcohol-induced decreased GSH availability in this extracellular pool. Thus maintenance of GSH in the ELF during chronic ethanol ingestion should protect against the ethanol-induced decreases in macrophage phagocytosis.…”

mentioning

confidence: 99%

Glutathione availability modulates alveolar macrophage function in the chronic ethanol-fed rat

Brown

Ping²,

Harris³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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113

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Brown LAS, Ping X-D, Harris FL, Gauthier TW. Glutathione availability modulates alveolar macrophage function in the chronic ethanol-fed rat. Am J Physiol Lung Cell Mol Physiol 292: L824-L832, 2007. First published November 22, 2006; doi:10.1152/ajplung.00346.2006.-We have previously demonstrated that chronic alcohol exposure decreases glutathione in the alveolar space. Although alcohol use is associated with decreased alveolar macrophage function, the mechanism by which alcohol impairs macrophage phagocytosis is unknown. In the current study, we examined the possibility that ethanol-induced alveolar macrophage dysfunction was secondary to decreased glutathione and subsequent chronic oxidative stress in the alveolar space. After 6 wk of ethanol ingestion, oxidant stress in the alveolar macrophages was evidenced by a 30-mV oxidation of the GSH/GSSG redox potential (P Յ 0.05). For control macrophages, ϳ80% internalized fluorescent Staphylococcus aureus were added in vitro. In contrast, only 20% of the macrophages from the ethanol-fed rats were able to bind and internalize fluorescent S. aureus. This ethanol-induced decreased capacity for phagocytosis was paralleled by increased apoptosis. When added to the ethanol diet, the glutathione precursors procysteine or N-acetyl cysteine normalized glutathione and oxidant stress in the epithelial lining fluid as well as the alveolar macrophages to control values. This attenuation of oxidant stress was associated with normalization of macrophage phagocytosis and viability. These results suggested that decreased glutathione availability in the alcoholic lung contribute to alveolar macrophage dysfunction via oxidative stress, resulting in not only decreased function but decreased viability. oxidative stress; apoptosis; lung; antioxidants A HISTORY OF CHRONIC ALCOHOL abuse increases the risk for infection, particularly in the lung (2). Although many mechanisms are undoubtedly involved, the increased risk of respiratory infections by alcoholics is partially due to an impaired immune response of the resident alveolar inflammatory cell, the alveolar macrophage. This impaired response is due in part to decreased ability of alveolar macrophages to phagocytose and clear infectious particles from the airways (3, 11). Equally important is impaired release of proinflammatory cytokines, chemokines, and oxidant radicals required for microbial killing (28).In the epithelial lining fluid (ELF) of the alveoli, the antioxidant glutathione (GSH) is essential for the detoxification of endogenous and exogenous oxidant radicals and protection of cells residing in the airway and alveolus. Under stressed conditions such as hyperoxia, the alveolar macrophage rely on the ELF pool of GSH to provide amino acids for de novo GSH synthesis (9), to protect themselves from oxidant injury (20) and maintain membrane integrity during their respiratory burst (30). Thus availability of extracellular GSH or its precursor amino acids is essential to maintain intracellular macrophage GSH homeostasis necessary for o...

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Chronic ethanol ingestion potentiates TNF-α-mediated oxidative stress and apoptosis in rat type II cells

Cited by 83 publications

References 45 publications

Maternal alcohol ingestion reduces surfactant protein A expression by preterm fetal lung epithelia

Maternal alcohol ingestion reduces surfactant protein A expression by preterm fetal lung epithelia

Zinc Deficiency Mediates Alcohol-Induced Alveolar Epithelial and Macrophage Dysfunction in Rats

Glutathione availability modulates alveolar macrophage function in the chronic ethanol-fed rat

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