Neutrophil Activation by Murine Retroviral Infection During Chronic Ethanol Consumption

Chen, Yinhong; Mendoza, Sam; Davis-Gorman, Grace; Cohen, Zoe; Gonzales, Raoul; Tuttle, Hillary A.; McDonagh, Paul F.; Watson, Ronald R.

doi:10.1093/alcalc/agg049

Cited by 9 publications

(7 citation statements)

References 24 publications

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“…The choice here of using doses of ethanol in quantities not toxic to liver was based on previous observations that mice exposed orally for a prolonged time to such a regimen did not suffer any visible damage to internal organs (30). This choice is indeed supported and extended by our study, which shows that at the dosage regimen used the mice did not suffer any metabolic consequences.…”

Section: Discussionsupporting

confidence: 58%

Ethanol prevents development of destructive arthritis

Jonsson

Verdrengh

Brisslert

et al. 2007

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

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Environmental factors are thought to play a major role in the development of rheumatoid arthritis. Because the use of ethanol is widespread, we assessed the role of ethanol intake on the propensity to develop chronic arthritis. Collagen type II-immunized mice were given water or water containing 10% (vol/vol) ethanol or its metabolite acetaldehyde. Their development of arthritis was assessed, as well as the impact of ethanol on leukocyte migration and activation of intracellular transcription factors. Mice exposed daily to this dose of ethanol did not display any liver toxicity, and the development of erosive arthritis was almost totally abrogated. In contrast, the antibody-mediated effector phase of collageninduced arthritis was not influenced by ethanol exposure. Also, the major ethanol metabolite, acetaldehyde, prevented the development of arthritis. This antiinflammatory and antidestructive property of ethanol was mediated by (i) down-regulation of leukocyte migration and (ii) up-regulation of testosterone secretion, with the latter leading to decreased NF-B activation. We conclude that low but persistent ethanol consumption delays the onset and halts the progression of collagen-induced arthritis by interaction with innate immune responsiveness.inflammation ͉ cytokines ͉ sex hormones ͉ antibodies ͉ immunity E xcessive alcohol consumption depresses the immune system and increases the propensity to severe bacterial infections, including pneumonia (1), tuberculosis (2), and bacterial peritonitis (3), and to viral infections (4-6). However, some epidemiological studies have suggested that light to moderate ethanol consumption has protective effects against several diseases including chronic heart diseases (7, 8) and ischemic stroke (9).Ethanol consumption has also been implicated in the pathogenesis of systemic lupus erythematosus (SLE), a complex autoimmune disease in the development of which environmental and genetic factors interact. Indeed, some investigators have found that exposure to ethanol is associated with a lower risk for developing SLE (10, 11), whereas others did not observe any effect of alcohol consumption on the incidence of SLE (12, 13). The association between ethanol and rheumatoid arthritis (RA) has been discussed in some studies, but definite conclusions could not be drawn (14-16). Studies so far have been of an epidemiological nature and therefore have not provided any hints about the biological mechanisms of environmental stimuli in the development of autoimmune disease. Our aim here was to assess whether low but persistent consumption of ethanol in quantities nontoxic to liver might affect the incidence and disease manifestation of collagen type II (CII)-induced arthritis (CIA), an established model of human RA. Our results suggest that ethanol intake delays the onset and halts the progression of destructive arthritis. Results Effect of Ethanol Consumption on Development of CIA.To assess whether ethanol drinking has any impact on the development of CIA, CII-immunized mice were provided w...

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Section: Discussionsupporting

confidence: 58%

Ethanol prevents development of destructive arthritis

Jonsson

Verdrengh

Brisslert

et al. 2007

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

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“…Peripheral blood neutrophils from infected gal3 −/− were compared to those from gal3 +/+ mice for the levels of activation marker CD11b ( 35 ). Results in Figure 6 A showed that CD11b on neutrophils from gal3 −/− mice were significantly higher than cells from gal3 +/+ mice after infection (Figure 6 A).…”

Section: Resultsmentioning

confidence: 99%

Cell Intrinsic Galectin-3 Attenuates Neutrophil ROS-Dependent Killing of Candida by Modulating CR3 Downstream Syk Activation

Huang

Chen

et al. 2017

Front. Immunol.

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Invasive candidiasis is a leading cause of nosocomial bloodstream infection. Neutrophils are the important effector cells in host resistance to candidiasis. To investigate the modulation of neutrophil fungicidal function will advance our knowledge on the control of candidiasis. While recombinant galectin-3 enhances neutrophil phagocytosis of Candida, we found that intracellular galectin-3 downregulates neutrophil fungicidal functions. Co-immunoprecipitation and immunofluorescence staining reveal that cytosolic gal3 physically interacts with Syk in neutrophils after Candida stimulation. Gal3−/− neutrophils have higher level of Syk activation as well as greater abilities to generate reactive oxygen species (ROS) and kill Candida than gal3+/+ cells. While galectin-3 deficiency modulates neutrophil and macrophage activation and the recruitment of monocytes and dendritic cells, the deficiency does not affect the numbers of infiltrating neutrophils or macrophages. Galectin-3 deficiency ameliorates systemic candidiasis by reducing fungal burden, renal pathology, and mortality. Adoptive transfer experiments demonstrate that cell intrinsic galectin-3 negatively regulates neutrophil effector functions against candidiasis. Reducing galectin-3 expression or activity by siRNA or gal3 inhibitor TD139 enhances human neutrophil ROS production. Mice treated with TD139 have enhanced ability to clear the fungus. Our work unravels the mechanism by which galectin-3 regulates Syk-dependent neutrophil fungicidal functions and raises the possibility that blocking gal3 in neutrophils may be a promising therapeutic strategy for treating systemic candidiasis.

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“…Less naïve Ag-specific T cell proliferation contributes to a poor adaptive immune response to pathogens and increased susceptibility to infection seen in alcoholism. In addition, marginal DC inflammatory cytokine production may also partially explain observed deficiencies in innate immunity following EtOH feeding as well (Boyadjieva et al, 2001; Chen et al, 2003; Frank et al, 2004; Laso et al, 1997; Laso et al, 2007b; Morio et al, 2000; Pan et al, 2006; Silvain et al, 1995). …”

Section: Discussionmentioning

confidence: 99%

Mechanisms by Which Chronic Ethanol Feeding Limits the Ability of Dendritic Cells to Stimulate T-Cell Proliferation

Fan

Edsen-Moore

Turner

et al. 2010

Alcoholism: Clinical and Experimental Research

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Background-As initiators of immune responses, dendritic cells (DCs) are required for antigen (Ag) specific activation of naïve T cells in the defense against infectious agents. The increased susceptibility to and severity of infection seen in chronic alcoholics could be due to impaired DC initiation of naïve T cell responses. Specifically, these DC may not provide adequate Signals 1 (Ag presentation), 2 (costimulation), or 3 (cytokine production) to these T cells.

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Neutrophil Activation by Murine Retroviral Infection During Chronic Ethanol Consumption

Cited by 9 publications

References 24 publications

Ethanol prevents development of destructive arthritis

Ethanol prevents development of destructive arthritis

Cell Intrinsic Galectin-3 Attenuates Neutrophil ROS-Dependent Killing of Candida by Modulating CR3 Downstream Syk Activation

Mechanisms by Which Chronic Ethanol Feeding Limits the Ability of Dendritic Cells to Stimulate T-Cell Proliferation

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