Inhibition of Human Natural Killer Cell Function in vitro by Glucose Concentrations Seen in Poorly Controlled Diabetes

Whalen, Margaret M.

doi:10.1159/000154852

Cited by 26 publications

(10 citation statements)

References 16 publications

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“…The ability of NK cells to lyse tumor cells was measured using a 51 Cr release assay (Whalen et al, 1999;Whalen, 1997). The target cell in all cytotoxicity assays was the NK-susceptible K562 (human chronic myelogenous leukemia) cell line.…”

Section: Cytotoxicity Assaymentioning

confidence: 99%

Effect of tributyltin (TBT) on ATP levels in human natural killer (NK) cells: Relationship to TBT‐induced decreases in NK function

Dudimah

Odman-Ghazi

Hatcher

et al. 2006

J of Applied Toxicology

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The purpose of this study was to investigate the role that tributyltin (TBT)-induced decreases in ATP levels may play in TBT-induced decreases in the tumor lysing (lytic) function of natural killer (NK) cells. NK cells are a subset of lymphocytes that act as an initial immune defense against tumor cells and virally infected cells. TBT is an environmental contaminant that has been detected in human blood, which has been shown to interfere with ATP synthesis. Previous studies have shown that TBT is able to decrease very significantly the lytic function of NK cells. In this study NK cells were exposed to various concentrations of TBT and to two other compounds that interfere with ATP synthesis (rotenone a complex I inhibitor and oligomycin an ATP synthase inhibitor) for various lengths of time before determining the levels of ATP and lytic function. Exposures of NK cells to 10, 25, 50 and 100 nm TBT did not significantly reduce ATP levels after 24 h. However, these same exposures caused significant decreases in cytotoxic function. Studies of brief 1 h exposures to a range of TBT, rotenone and oligomycin concentrations followed by 24 h, 48 h and 6 day periods in compound-free media prior to assaying for ATP levels or cytotoxic function showed that each of the compounds caused persistent decreases in ATP levels and lytic function of NK cells. Exposures to 0.05-5 microm rotenone or oligomycin for 1 h reduced ATP levels by 20-25% but did not have any measurable effect on the ability of NK cells to lyse tumor cells. ATP levels were also decreased by about 20-25% after 24 h or 48 h exposures to rotenone or oligomycin (0.5 microm ), and the lytic function was decreased by about 50%. The results suggest that TBT-induced decreases in ATP levels were not responsible for the loss of cytotoxic function seen at 1 h and 24 h. However, TBT-induced decreases of NK-ATP levels may be at least in part responsible for losses of NK-cytotoxic function seen after 48 h and 6 day exposures.

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Section: Cytotoxicity Assaymentioning

confidence: 99%

Effect of tributyltin (TBT) on ATP levels in human natural killer (NK) cells: Relationship to TBT‐induced decreases in NK function

Dudimah

Odman-Ghazi

Hatcher

et al. 2006

J of Applied Toxicology

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“…NK cytotoxicity was measured using a 51 Cr release assay (Whalen et al, 1997(Whalen et al, , 1999. The target cells in all cytotoxicity assays were cells of the NK-susceptible K562 (human chronic myelogenous leukemia) cell line.…”

Section: Chromium Release Assaymentioning

confidence: 99%

Persistent inhibition of human natural killer cell function by ziram and pentachlorophenol

2005

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Ziram is a currently used agricultural fungicide. It is also used as an additive in the production of latex gloves. Because of these uses, there is a potential for human exposure to this compound. Pentachlorophenol (PCP) has been used as an insecticide, fungicide, disinfectant, and ingredient in antifouling paints. Currently, it is used as a wood preservative for power-line poles and fence posts. Measurable levels of PCP have been detected in human blood and urine. In previous studies we demonstrated that both these compounds could cause very significant inhibition of the tumor-killing function of human natural killer (NK) cells. NK lymphocytes play a central role in immune defense against viral infection and the formation of primary tumors. So interference with their function could increase the risk of tumor development. In the present study we examined the effects of exposure to ziram or PCP of brief duration (1 h) on the ability of NK cells to destroy tumor cells. NK cells were exposed to either ziram (5-0.5 microM) or PCP (10-5 microM) for 1 h followed by 0 h, 24 h, 48 h, or 6 days in compound-free media and then were tested for the ability to lyse as well as to bind tumor cells. A 1-h exposure to as little as 2.5 microM ziram decreased the ability of NK cells to lyse target tumor cells, which persisted up to 6 days following exposure. The loss of lytic function for from 24 h to 6 days following exposure was accompanied by a comparable loss of NK capacity to bind tumor cells. Exposure to 10 microM PCP for 1 h caused a progressive loss (greater than 80%) of lytic function within 6 days of exposure. In contrast to ziram, PCP exposure caused no accompanying loss of binding function.

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“…NK cytotoxicity was measured using a 51 Cr release assay (Whalen, 1997;Whalen et al, 1999). The target cell in all cytotoxicity assays was the NK-susceptible K562 (human chronic myelogenous leukemia) cell line.…”

Section: Chromium Release Assaymentioning

confidence: 99%

Effects of in vitro exposure to low levels of organotin and carbamate pesticides on human natural killer cell cytotoxic function

Wilson

Dzon

Reed

et al. 2004

Environmental Toxicology

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Human natural killer (NK) lymphocytes play a central role in immune system defense against viral infection and against the formation of primary tumors. Organotin (OT) pesticides have been used in industrial and agricultural applications, and OT contamination has been reported in water, sediment, and fish. Carbamate pesticides are currently used in agricultural chemicals. Two specific carbamates used in agriculture are ziram and maneb; ziram also is used as an additive in rubber products including latex gloves. In previous studies we demonstrated that at concentrations in the 150-200 nM range, the OTs tributyltin (TBT) and triphenyltin (TPT) were capable of disrupting the function of human NK cells after incubations to as short as 24 h. Previously, we also examined the effects of ziram and maneb at higher concentrations on the cytotoxic function of human NK cells. The current study examined the effects of exposure of up to 6 days to lower concentrations of each of these compounds on the cytotoxic function of NK cells. The OTs were studied at concentrations ranging from 200 to 10 nM; ziram was studied at concentrations of 2.5 microM-125 nM and maneb at concentrations of 10-1 microM. These conditions were studied both in highly purified NK cells and in a mixture of lymphocytes containing both T and NK cells. As little as 25 nM TBT decreased the function of purified NK cells after 24 and 48 h, whereas 10 nM TBT was effective after 6 days. The lowest level of TPT that was effective at 24 h was 50 nM whereas the results after 48 h and 6 days were similar to those seen with TBT. The presence of T lymphocytes diminished the effects of both TBT and TPT on NK cytotoxic function. A concentration of ziram as low as 125 nM produced significant loss of cytotoxic function in highly purified NK cells (65% decrease in function after 6 days). The toxicity of each of the compounds studied increased very significantly with length of exposure.

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Inhibition of Human Natural Killer Cell Function in vitro by Glucose Concentrations Seen in Poorly Controlled Diabetes

Cited by 26 publications

References 16 publications

Effect of tributyltin (TBT) on ATP levels in human natural killer (NK) cells: Relationship to TBT‐induced decreases in NK function

Effect of tributyltin (TBT) on ATP levels in human natural killer (NK) cells: Relationship to TBT‐induced decreases in NK function

Persistent inhibition of human natural killer cell function by ziram and pentachlorophenol

Effects of in vitro exposure to low levels of organotin and carbamate pesticides on human natural killer cell cytotoxic function

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