Natural Killer (NK) Cell Lytic Dysfunction and Putative NK Cell Receptor Expression Abnormality in Members of a Family With Chromosome 3p-Linked von Hippel-Lindau Disease

Ortaldo, John R.; Young, Howard A.; Frey, Joyce L.

doi:10.1093/jnci/84.24.1897

Cited by 8 publications

(5 citation statements)

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“…Previous studies have indicated that humans with a defect that leaves their NK cells unable to lyse target cells have a predisposition to development of certain tumors (Ortaldo et al, 1992) and that individuals lacking NK cells had severe herpes virus infection (Biron et al, 1989) and Epstein-Bar infections (Fleisher, et al, 1982). Studies in mice have shown that a decrease in NK cell activity of 80% results in an increase in tumor formation upon challenge with melanoma cells (Wilson et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Tetrabromobisphenol A has immunosuppressive effects on human natural killer cells

Kibakaya

Stephen

Whalen

2009

Journal of Immunotoxicology

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Human natural killer (NK) cells are lymphocytes that destroy tumor cells, virally infected cells, and antibody-coated cells. Tetrabromobisphenol A (TBBPA) is used both as a reactive and an additive flame retardant in a variety of materials and appears to contaminate the environment. TBBPA has been found in human blood samples and if it interferes with NK cell function, this could increase risk of tumor development and/or viral infection. This study examines the effects of exposure to various concentrations of TBBPA for 24 hr, 48 hr, and 6 d on the lytic function, tumor-target-binding function, and ATP levels of NK cells. These same parameters were also monitored in NK cells that were exposed to TBBPA for 1 hr followed by 24 hr, 48 hr, and 6 d in TBBPA-free media. A 24 hr exposure of NK cells to 5 μM TBBPA caused a greater than 95% decrease in NK lytic function, a 70% decrease in binding function, and a 34% decrease in ATP levels in NK cells. Exposure to 2.5 μM TBBPA for 24 hr decreased lytic function by 76%, binding function by 20%, and had no effect on ATP levels. Exposure of NK cells to 5 μM TBBPA for 1 hr followed by 24 hr in TBBPA-free media caused a progressive and persistent loss of lytic function (41%) while not affecting either binding ability or ATP levels. The results indicate that TBBPA exposures decrease the lytic function of human NK cells and that an initial brief (1 hr) exposure can cause a progressive loss of function. Additionally, the data also indicate that TBBPA-induced loss of NK lytic function can occur at concentration of TBBPA that do not affect target-binding ability and ATP levels of NK cells.

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Section: Discussionmentioning

confidence: 99%

Tetrabromobisphenol A has immunosuppressive effects on human natural killer cells

Kibakaya

Stephen

Whalen

2009

Journal of Immunotoxicology

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“…Their importance in preventing cancers and viral infections has been shown both in humans and in animal models (Ortaldo, et al, 1992; Purdy and Campbell, 2009; Ballas et al, 1990; Fulton et al, 1984; Makrigiannis and Anderson, 2003; Mishra et al, 2010). They are known to secrete TNFα as well as other cytokines and this is also a significant part of their important immune function.…”

Section: Introductionmentioning

confidence: 99%

Tributyltin and dibutyltin alter secretion of tumor necrosis factor alpha from human natural killer cells and a mixture of T cells and natural killer cells

Hurt

Hurd-Brown

Whalen

2012

J of Applied Toxicology

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Butyltins (BTs) have been in widespread use. Tributyltin (TBT) has been used as a biocide in a variety of applications and is found in human blood samples. Dibutyltin (DBT) has been used as a stabilizer in polyvinyl chloride plastics and as a de-worming agent in poultry. DBT, like TBT, is found in human blood. Human natural killer (NK) cells are the earliest defense against tumors and viral infections and secrete the cytokine tumor necrosis factor (TNF) alpha (α). TNFα is an important regulator of adaptive and innate immune responses. TNFα promotes inflammation and an association between malignant transformation and inflammation has been established. Previously, we have shown that TBT and DBT were able to interfere with the ability of NK cells to lyse tumor target cells. Here we show that BTs alter cytokine secretion by NK cells as well as a mixture of T and NK lymphocytes (T/NK cells). We examined 24 h, 48 h, and 6 day exposures to TBT (200- 2.5 nM) and DBT (5- 0.05 µM) on TNFα secretion by highly enriched human NK cells and T/NK cells. The results indicate that TBT (200 - 2.5 nM) decreased TNFα secretion from NK cells. In the T/NK cells 200 nM TBT decreased secretion while 100-5 nM TBT increased secretion of TNFα. NK cells or T/NK cells exposed to higher concentrations of DBT showed decreased TNFα secretion while lower concentrations showed increased secretion. The effects of BTs on TNFα secretion are seen at concentrations present in human blood.

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“…When NK function is decreased in mice, it results in increased tumor formation (Wilson et al, 2001). Humans with defective NK cells have been shown to have an increased risk of developing certain tumors (Ortaldo et al, 1992) and individuals with absent or compromised NK lymphocytes experienced severe herpes virus and Epstein-Barr virus infections (Biron et al, 1989; Fleisher, et al, 1982). Compromise of NK cell function by chemical contaminant exposure could then lead to increased risk of both tumor development as well as viral infection as evidenced by decreased NK cell function resulting in increased tumor metastases in mice exposed to cigarette smoke (Lu et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Brominated flame retardants, tetrabromobisphenol A and hexabromocyclododecane, activate mitogen-activated protein kinases (MAPKs) in human natural killer cells

et al. 2014

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NK cells provide a vital surveillance against virally infected cells, tumor cells, and antibody-coated cells through the release of cytolytic mediators and gamma interferon (IFN-γ). Hexabromocyclododecane (HBCD) is a brominated flame retardant used primarily in expanded (EPS) and extruded (XPS) polystyrene foams for thermal insulation in the building and construction industry. Tetrabromobisphenol A (TBBPA) is used both as a reactive and an additive flame retardant in a variety of materials. HBCD and TBBPA contaminate the environment and are found in human blood samples. In previous studies, we have shown that other environmental contaminants, such as the dibutyltin (DBT) and tributyltin (TBT), decrease NK lytic function by activating mitogen-activated protein kinases (MAPKs) in the NK cells. HBCD and TBBPA also interfere with NK cell(s) lytic function. The current study evaluates whether HBCD and/or TBBPA have the capacity to activate MAPKs and MAPK kinases (MAP2Ks). The effects of concentrations of HBCD and TBBPA that inhibited lytic function on the phosphorylation state and total levels of the MAPKs (p44/42, p38, and JNK) and the phosphorylation and total levels of the MAP2Ks (MEK1/2 and MKK3/6) were examined. Results indicate that exposure of human NK cells to 10-0.5 µM HBCD or TBBPA activate MAPKs and MAP2Ks. This HBCD and TBBPA-induced activation of MAPKs may leave them unavailable for activation by virally infected or tumor target cells and thus contributes to the observed decreases in lytic function seen in NK cells exposed to HBCD and TBBPA.

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Natural Killer (NK) Cell Lytic Dysfunction and Putative NK Cell Receptor Expression Abnormality in Members of a Family With Chromosome 3p-Linked von Hippel-Lindau Disease

Cited by 8 publications

References 0 publications

Tetrabromobisphenol A has immunosuppressive effects on human natural killer cells

Tetrabromobisphenol A has immunosuppressive effects on human natural killer cells

Tributyltin and dibutyltin alter secretion of tumor necrosis factor alpha from human natural killer cells and a mixture of T cells and natural killer cells

Brominated flame retardants, tetrabromobisphenol A and hexabromocyclododecane, activate mitogen-activated protein kinases (MAPKs) in human natural killer cells

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