Exposure to sodium tungstate and Respiratory Syncytial Virus results in hematological/immunological disease in C57BL/6J mice

Fastje, Cynthia D.; Harper, Kevin; Terry, Chad; Sheppard, Paul R.; Witten, Mark L.

doi:10.1016/j.cbi.2011.04.008

“…In the present study, the functional activity of T CTL cells decreased at 1000 mg STD/L when splenic T CTL lymphocytes from control and STD-treated mice were sensitized to P815 mastocytoma cells ex vivo , prior to functional assessment in the effector phase. Similarly, other studies have shown that tungstate-treated C57BL/6 mice developed significant splenomegaly when inoculated with the T-cell activating RSV (Fastje et al, 2012), and demonstrated suppression of activated T H and T CTL cells, when challenged with SEB (Osterburg et al, 2014). In the absence of RVS or SEB challenge, tungstate had no effect on spleen size or T-cell populations (Fastje et al, 2012; Osterburg et al, 2014).…”

Section: Discussionmentioning

confidence: 65%

“…Similarly, other studies have shown that tungstate-treated C57BL/6 mice developed significant splenomegaly when inoculated with the T-cell activating RSV (Fastje et al, 2012), and demonstrated suppression of activated T H and T CTL cells, when challenged with SEB (Osterburg et al, 2014). In the absence of RVS or SEB challenge, tungstate had no effect on spleen size or T-cell populations (Fastje et al, 2012; Osterburg et al, 2014). Exposure to tungsten in drinking water was also associated with increased tumor burden in BALB/c mice treated with 66Cl4 tumor cells (Bolt et al, 2015).…”

Section: Discussionmentioning

confidence: 65%

“…Published reports indicated that sodium tungstate may modulate hematopoiesis, immune cell populations, and immune responses in rodent models (Osterburg et al, 2010, 2014; Fastje et al, 2012). …”

Section: Discussionmentioning

confidence: 99%

“…Although evidence is limited, rodent studies suggest that tungsten exposure may affect the immune system, as indicated by localization of tungsten in bone and spleen (McDonald et al, 2007; Guandalini et al, 2011; Kelly et al, 2013); attenuation of the delayed-type hypersensitivity response; alteration of T-cell populations (Osterburg et al, 2014); transcriptomic changes associated with regulation of some immune responses and hematological/immunological disease (Fastje et al, 2008, 2009); and, induction of splenomegaly and neutrophilia following co-exposure to sodium tungstate and respiratory syncytial virus (RSV) (Fastje et al, 2012). Published reports indicated that sodium tungstate dysregulated cytokine production, the cell cycle, and apoptosis in human peripheral blood lymphocytes (Osterburg et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Immunotoxic effects of sodium tungstate dihydrate on female B₆C₃F₁/N mice when administered in drinking water

Frawley

¹

,

Smith

²

,

White

³

et al. 2016

Journal of Immunotoxicology

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Tungsten is a naturally occurring, high tensile strength element that has been used in a number of consumer products. Tungsten has been detected in soil, waterways, groundwater, and human tissue and body fluids. Elevated levels of tungsten in urine were reported for populations exposed to tungstate in drinking water in areas where natural tungsten formations were prevalent. Published reports indicated that sodium tungstate may modulate hematopoiesis, immune cell populations, and immune responses in rodent models. The objective of this study was to assess potential immunotoxicity of sodium tungstate dihydrate (STD), a drinking water contaminant. Female B6C3F1/N mice received 0–2000 mg STD/L in their drinking water for 28 days, and were evaluated for effects on immune cell populations in spleen and bone marrow, and humoral-mediated, cell-mediated, and innate immunity. Three different parameters of cell-mediated immunity were similarly affected at 1000 mg STD/L. T-cell proliferative responses against allogeneic leukocytes and anti-CD3 were decreased 32%, and 21%, respectively. Cytotoxic T-lymphocyte activity was decreased at all effector:target cell ratios examined. At 2000 mg STD/L, the absolute numbers of CD3+ T-cell progenitor cells in bone marrow were increased 86%, but the alterations in B-lymphocyte and other progenitor cells were not significant. There were no effects on bone marrow DNA synthesis or colony forming capabilities. STD-induced effects on humoral-mediated immunity, innate immunity, and splenocyte sub-populations were limited. Enhanced histopathology did not detect treatment-related lesions in any of the immune tissues. These data suggest exposure to STD in drinking water may adversely effect cell-mediated immunity.

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“…In addition, the ROS produced by XO have been shown to contribute to host defenses in microbial infection models (Umezawa et al, 1997;Vorbach et al, 2003). Tungstate inhibition of XO in mice increased the susceptibility to leukemic outcomes when coupled with respiratory syncytial virus (RSV) exposure (Fastje et al, 2011). While the mechanism of the leukemic transformation is unclear, recent data demonstrate that XO-dependent ROS have a central role in antigen presentation and cell maturation of Kupffer cells and other professional antigen-presenting cells (APC) (Maemura et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Oral tungstate (Na₂WO₄) exposure reduces adaptive immune responses in mice after challenge

Osterburg

¹

,

Robinson

²

,

Mokashi

³

et al. 2013

Journal of Immunotoxicology

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Tungstate (WO²⁻₄) has been identified as a ground water contaminant at military firing ranges and can be absorbed by ingestion. In this study, C57BL6 mice were exposed to sodium tungstate (Na2WO4·2H2O) (0, 2, 62.5, 125, and 200 mg/kg/day) in their drinking water for an initial 28-day screen and in a one-generation (one-gen) model. Twenty-four hours prior to euthanasia, mice were intraperitoneally injected with Staphylococcal enterotoxin B (SEB) (20 μg/mouse) or saline as controls. After euthanasia, splenocytes and blood were collected and stained with lymphocyte and/or myeloid immunophenotyping panels and analyzed by flow cytometry. In the 28-day and one-gen exposure, statistically significant reductions were observed in the quantities of activated cytotoxic T-cells (TCTL; CD3(+)CD8(+)CD71(+)) and helper T-cells (TH; CD3(+)CD4(+)CD71(+)) from spleens of SEB-treated mice. In the 28-day exposures, CD71(+) TCTL cells were 12.87 ± 2.05% (SE) in the 0 tungstate (control) group compared to 4.44 ± 1.42% in the 200 mg/kg/day (p < 0.001) group. TH cells were 4.85 ± 1.23% in controls and 2.76 ± 0.51% in the 200 mg/kg/day (p < 0.003) group. In the one-gen exposures, TCTL cells were 7.98 ± 0.49% and 6.33 ± 0.49% for P and F1 mice after 0 mg/kg/day tungstate vs 1.58 ± 0.23% and 2.52 ± 0.25% after 200 mg/kg/day of tungstate (p < 0.001). Similarly, TH cells were reduced to 6.21 ± 0.39% and 7.20 ± 0.76%, respectively, for the 0 mg/kg/day P and F1 mice, and 2.28 ± 0.41% and 2.85 ± 0.53%, respectively, for the 200 mg/kg/day tungstate P and F1 groups (p < 0.001). In delayed-type hypersensitivity Type IV experiments, tungstate exposure prior to primary and secondary antigen challenge significantly reduced footpad swelling at 20 and 200 mg/kg/day. These data indicate that exposure to tungstate can result in immune suppression that may, in turn, reduce host defense against pathogens.

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Tungsten, Tungsten Alloys, and Tungsten Compounds

Trasorras

¹

,

Wolfe

²

,

Knabl

³

et al. 2016

Ullmann's Encyclopedia of Industrial Chemistry

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The article contains sections titled: 1. Introduction 2. Properties 2.1. Physical Properties 2.2. Chemical Properties 3. Raw Materials 3.1. Natural Resources 3.2. Tungsten Scrap 4. Production 4.1. Mining and Ore Beneficiation 4.2. Pretreatment of Ore Concentrates and Scrap 4.3. Hydrometallurgy 4.3.1. Digestion 4.3.2. Purification 4.3.3. Conversion of Sodium Tungstate Solution to Ammonium Tungstate Solution 4.3.4. Crystallization of Ammonium Paratungstate (APT) 4.4. Production of Tungsten Oxides 4.5. Production of Tungsten Metal Powder 4.6. Production of High‐Purity Tungsten Metal (99.999 ‐ 99.9999%) 4.7. Powder Metallurgy (PM) 4.8. Metal Injection Molding 4.8.1 MIM Process Overview 4.8.2 General Guidelines 4.8.3 MIM of Tungsten, Tungsten Alloys, Tungsten–Copper Composites, Tungsten Heavy Alloy, and Cemented Carbide 4.9. Additive Manufacturing of Tungsten and Cemented Carbides (WC–Co) 4.10. Fabrication of Wrought PM Tungsten 4.10.1. Shaping–Mill Products 4.10.2 Mechanical Bonding of Tungsten to Tungsten and Other Metals 4.11. Surface Treatment 4.12. Melting 5. Tungsten Alloys 5.1. Single‐Phase Solid‐Solution Alloys 5.2. Multiphase Alloys 5.2.1 Tungsten Heavy Metals 5.2.2. Tungsten–Copper and Tungsten–Silver Composites 5.2.3. Non‐Sag Tungsten 5.2.4 Alloys with Oxide Dispersions 5.2.5 Porous, Infiltrated Tungsten 6. Uses of Tungsten 6.1. Tungsten and Tungsten Alloys 6.2. Cemented Carbides (WC–Co) 6.3. Tungsten Coatings 7. Tungsten in Melting Metallurgy of Steel and Superalloys 7.1. Tungsten in Steel 7.2. Tungsten in Superalloys 7.3. Master Alloys 7.3.1 Ferrotungsten 7.3.2. Tungsten Melting Base 7.3.3. Master Alloys for Superalloys 7.4. Production of Master Alloys 7.4.1. Production of Ferrotungsten 7.4.2. Production of Tungsten Melting Base 7.4.3. Production of Master Alloys for Superalloys 8. Tungsten Compounds and Their Application 8.1. Tungsten Chemistry 8.2. Aqueous Solutions of Tungsten 8.3. Intermetallic Compounds 8.4. Compounds with Nonmetals 8.4.1. Tungsten–Boron Compounds 8.4.2. Tungsten–Carbon Compounds 8.4.3. Tungsten–Silicon Compounds 8.4.4. Tungsten–Group 15 Compounds 8.4.5. Tungsten–Oxygen Compounds 8.4.6. Tungsten–Chalcogenide Compounds 8.4.7. Tungsten–Halogenide Compounds 9. Tungsten in Catalysis 10. Tungsten Recycling 10.1. Direct Recycling 10.2. Semi‐Direct Methods 10.3. Hydrometallurgy 10.4. Melting Metallurgy 11. Analysis 11.1. Raw Materials 11.2. High Purity Intermediate Products, Tungsten Powder and Sintered Tungsten Metal 11.3 Trace Elements in High‐Purity Tungsten Metal 12. Economic Aspects 12.1. Production 12.2. Consumption 12.3 Price 13. Toxicology and Occupational Health 13.1. Toxicokinetics 13.2. Acute Toxicity 13.3. Subchronic and Chronic Toxicity 13.4. Genotoxicity 13.5. Carcinogenicity 13.6. Reproductive Toxicity 13.7. Developmental Toxicity 13.8. Immunotoxicity 13.9. Human Biomonitoring Data 13.10. Occupational Health 14. Acknowledgements

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Exposure to sodium tungstate and Respiratory Syncytial Virus results in hematological/immunological disease in C57BL/6J mice

Cited by 15 publications

References 33 publications

Immunotoxic effects of sodium tungstate dihydrate on female B₆C₃F₁/N mice when administered in drinking water

Immunotoxic effects of sodium tungstate dihydrate on female B₆C₃F₁/N mice when administered in drinking water

Oral tungstate (Na₂WO₄) exposure reduces adaptive immune responses in mice after challenge

Tungsten, Tungsten Alloys, and Tungsten Compounds

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Exposure to sodium tungstate and Respiratory Syncytial Virus results in hematological/immunological disease in C57BL/6J mice

Cited by 15 publications

References 33 publications

Immunotoxic effects of sodium tungstate dihydrate on female B6C3F1/N mice when administered in drinking water

Immunotoxic effects of sodium tungstate dihydrate on female B6C3F1/N mice when administered in drinking water

Oral tungstate (Na2WO4) exposure reduces adaptive immune responses in mice after challenge

Tungsten, Tungsten Alloys, and Tungsten Compounds

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Immunotoxic effects of sodium tungstate dihydrate on female B₆C₃F₁/N mice when administered in drinking water

Immunotoxic effects of sodium tungstate dihydrate on female B₆C₃F₁/N mice when administered in drinking water

Oral tungstate (Na₂WO₄) exposure reduces adaptive immune responses in mice after challenge