Modulation of Perforin, Granzyme A, and Granzyme B in Murine Natural Killer (NK), IL2 Stimulated NK, and Lymphokine-Activated Killer Cells by Alcohol Consumption

Spitzer, Jessica H.; Meadows, Gary G.

doi:10.1006/cimm.1999.1511

Cited by 35 publications

(22 citation statements)

References 31 publications

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“…Studies in mice (Collier and Pruett, 2000) showed decreased levels of granzyme B and perforin and decreased production and response of IFN-␣ as factors involved in diminished activation of NK cell lytic function in mice that were administered ethanol intragastrically by gavage as a 32% v/v solution in tissue culture grade water. Spitzer and Meadows (1999) also showed that alcohol consumption suppresses NK and lymphokine-activated killer cell cytolytic activity in mice involving the collective reduction of target-induced release, activity, and expression of perforin and the granular proteases granzymes A and B. It is interesting to note that, as in mice, ethanol reduced both the mRNA and protein levels of perforin, granzymes, and IFN-␥ in rat spleens.…”

Section: Discussionmentioning

confidence: 87%

“…One million splenic lymphocyte cells were lysed with 0.1% Triton X-100 (Rohm & Haas Co., Philadelphia, PA; in 100 mM Tris-HCl, kept on ice for 1 hr and centrifuged at 10,000 ϫ g for 15 min; Spitzer and Meadows, 1999). Fifty milliliters of sample supernatant was added to 150 l of a freshly made reaction mixture of 0.2 mM t-butoxycarbonyl-Ala-Ala-Asp-S-Bzl (BAADT; Enzyme System Products, Livermore, CA) and 0.2 mM Ellman's reagent (Sigma) in Buffer A and incubated for 30 min.…”

Section: Granzyme B Activitymentioning

confidence: 99%

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Reduction of Perforin, Granzyme B, and Cytokine Interferon γ by Ethanol in Male Fischer 344 Rats

Dokur¹,

Boyadjieva²,

Sarkar³

2003

Alcoholism Clin & Exp Res

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Section: Discussionmentioning

confidence: 87%

Section: Granzyme B Activitymentioning

confidence: 99%

Reduction of Perforin, Granzyme B, and Cytokine Interferon γ by Ethanol in Male Fischer 344 Rats

Dokur¹,

Boyadjieva²,

Sarkar³

2003

Alcoholism Clin & Exp Res

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“…Based on the work of Meadows and colleagues, we have established an EtOH-in-drinking-water mouse model of chronic alcohol intake (hereafter referred to as the Meadows-Cook model) (16, 17, 20, 21). Importantly, this model results in a range of immune and tissue lesions that are normally observed in chronic alcoholics without inducing an overt stress response (16).…”

Section: Resultsmentioning

confidence: 99%

Chronic Alcohol Consumption Increases the Severity of Murine Influenza Virus Infections

Meyerholz¹,

Edsen-Moore²,

McGill

et al. 2008

The Journal of Immunology

134

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Respiratory infections with both seasonal as well as potential pandemic Influenza viruses represent a significant burden on human health. Furthermore, viruses such as Influenza are increasingly recognized as important etiologic agents in community acquired pneumonia. Within the United States alone ~12.9 million people are heavy drinkers and chronic abuse of alcohol is known to increase the risk and severity of community acquired pneumonia. Given the lack of knowledge regarding Influenza disease in this population, we determined the effects of chronic alcohol consumption on Influenza virus infection. Herein, we report that mice exposed to chronic ethanol have sharp increases in morbidity, mortality, and pulmonary virus titers relative to controls. These increases in influenza severity correspond with inhibited pulmonary influenza-specific CD8 T cell responses. Further, chronic ethanol consumption results in an enhanced pulmonary lesion severity, similar to that recently described for pandemic influenzas. Together, our results suggest that chronic alcohol consumption may increase the risk for severe influenza virus infections by altering the pulmonary inflammatory environment and CD8 T cell response.

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“…Mice receiving alcohol were given increasing concentrations of alcohol in water over a 2-week period until the target concentration of 20% was reached using the Meadows-Cook model [27,28]. Mice in the alcohol group were given 5% alcohol (wt/vol) to drink ad libitum and scaled up over two weeks to 20% alcohol (wt/vol) for 6 weeks [30].…”

Section: Methodsmentioning

confidence: 99%

Alcohol Exposure Alters Mouse Lung Inflammation in Response to Inhaled Dust

et al. 2012

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Alcohol exposure is associated with increased lung infections and decreased mucociliary clearance. Occupational workers exposed to dusts from concentrated animal feeding operations (CAFOs) are at risk for developing chronic inflammatory lung diseases. Agricultural worker co-exposure to alcohol and organic dust has been established, although little research has been conducted on the combination effects of alcohol and organic dusts on the lung. Previously, we have shown in a mouse model that exposure to hog dust extract (HDE) collected from a CAFO results in the activation of protein kinase C (PKC), elevated lavage fluid cytokines/chemokines including interleukin-6 (IL-6), and the development of significant lung pathology. Because alcohol blocks airway epithelial cell release of IL-6 in vitro, we hypothesized that alcohol exposure would alter mouse lung inflammatory responses to HDE. To test this hypothesis, C57BL/6 mice were fed 20% alcohol or water ad libitum for 6 weeks and treated with 12.5% HDE by intranasal inhalation method daily during the final three weeks. Bronchoalveolar lavage fluid (BALF), tracheas and lungs were collected. HDE stimulated a 2–4 fold increase in lung and tracheal PKCε (epsilon) activity in mice, but no such increase in PKCε activity was observed in dust-exposed mice fed alcohol. Similarly, alcohol-fed mice demonstrated significantly less IL-6 in lung lavage in response to dust than that observed in control mice instilled with HDE. TNFα levels were also inhibited in the alcohol and HDE-exposed mouse lung tissue as compared to the HDE only exposed group. HDE-induced lung inflammatory aggregates clearly present in the tissue from HDE only exposed animals were not visually detectable in the HDE/alcohol co-exposure group. Statistically significant weight reductions and 20% mortality were also observed in the mice co-exposed to HDE and alcohol. These data suggest that alcohol exposure depresses the ability of the lung to activate PKCε-dependent inflammatory pathways to environmental dust exposure. These data also define alcohol as an important co-exposure agent to consider in the study of inhalation injury responses.

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Modulation of Perforin, Granzyme A, and Granzyme B in Murine Natural Killer (NK), IL2 Stimulated NK, and Lymphokine-Activated Killer Cells by Alcohol Consumption

Cited by 35 publications

References 31 publications

Reduction of Perforin, Granzyme B, and Cytokine Interferon γ by Ethanol in Male Fischer 344 Rats

Reduction of Perforin, Granzyme B, and Cytokine Interferon γ by Ethanol in Male Fischer 344 Rats

Chronic Alcohol Consumption Increases the Severity of Murine Influenza Virus Infections

Alcohol Exposure Alters Mouse Lung Inflammation in Response to Inhaled Dust

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