Lead and cadmium at very low doses affect in vitro immune response of human lymphocytes

Borella, Paola; Giardino, A.

doi:10.1016/s0013-9351(05)80173-2

Cited by 47 publications

(10 citation statements)

References 30 publications

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“…Highly relevant to the presence of autoantibodies are studies indicating that low levels of lead enhance immunoglobulin synthesis (86,92 In the nervous system, astrocytes act as sites of deposition for heavy metals, including mercury (96,97) and lead (98,99), where these metals may modulate metabolic function (100,101). In this regard, astrocytes may themselves be targets of lead and mercury, resulting in their degeneration and death, whether as a primary target or secondary to astrogliosis (102)(103)(104)(105)(106).…”

Section: Neurocytology Immunology and Immunoprivilegementioning

confidence: 99%

Neuroimmunotoxicology: Humoral Assessment of Neurotoxicity and Autoimmune Mechanisms

El-Fawal¹,

Waterman²,

Feo³

et al. 1999

Environmental Health Perspectives

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The interactions between the nervous and immune systems have been recognized in the development of neurodegenerative disease. This can be exploited through detection of the immune response to autoantigens in assessing the neurotoxicity of environmental chemicals. To test this hypothesis, the following questions were addressed. a) Are autoantibodies to nervous system (NS) antigens detected in populations exposed to environmental or occupational chemicals? In sera of male workers exposed to lead or mercury, autoantibodies, primarily IgG, to neuronal cytoskeletal proteins, neurofilaments (NFs), and myelin basic protein (MBP) were prevalent. These findings were confirmed in mice and rats exposed to either metal. b) Do autoantibodies to NS antigens relate to indices of exposure? In humans exposed to either metal, and similarly in exposed rats, titers of lgG against NFs and MBP significantly correlated with blood lead or urinary mercury, the typical indices of exposure. c) Do autoantibodies correlate with sensorimotor deficits? In workers exposed to lead or mercury, a significant correlation was observed between lgG titers and subclinical deficits. Doses of metals used in rat exposures were subclinical, suggesting that autoantibodies may be predictive of neurotoxicity. d) Is the detection indicative of nervous system pathology? In rats exposed to metals, histopathology indicated central nervous system (CNS) and peripheral nervous system (PNS) damage. In addition there was evidence of astrogliosis, which is indicative of neuronal damage in the CNS, and the presence of lgG concentrated along the blood-brain barrier, as indicated by immunostaining for antibodies. e) Are immune responses to NS antigens pathogenic? Immunoglobulin fractions from rat and human sera interfered with neuromuscular function. These studies suggest that the detection of autoantibodies to NS-specific antigens may be used to monitor the development of neurotoxicity to environmental chemicals and that immune mechanisms may be involved in the progression of neurodegeneration.

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Section: Neurocytology Immunology and Immunoprivilegementioning

confidence: 99%

Neuroimmunotoxicology: Humoral Assessment of Neurotoxicity and Autoimmune Mechanisms

El-Fawal¹,

Waterman²,

Feo³

et al. 1999

Environmental Health Perspectives

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“…4C) showed suppressive and stimulative effects on IgM production, respectively, well correspondent with reported findings. 5,11) Different from the stimulatory effect reported else, 6) chlorpromazine produced enhancement of neither cell proliferation nor IgM production induced by PWM. When compared with human PBMC, mouse spleen cells may be less sensitive to the stimulatory effect of this compound, because suppressive effect of the compound at higher concentrations was observed in mouse spleen cell cultures as well as human PBMC cultures.…”

Section: Discussionmentioning

confidence: 86%

A Simple Bioassay for Evaluating Immunotoxic Properties of Chemicals by Use of in Vitro Antibody Production System.

Takahashi

Ohsawa

Utsumi

2002

JOURNAL OF HEALTH SCIENCE

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Antibody production is one of biomarkers sensitive to chemical toxicity. A simple assay system for evaluating toxic effect of chemicals on antibody production was developed using pokeweed mitogen (PWM)-induced IgM production by spleen cell cultures obtained from BALB/c mice. It was evaluated with reference immunomodulating chemicals. Cultured spleen cells significantly and day-dependently produced IgM after PWM stimulation. Test chemicals were added to the cultures simultaneousely with PWM. At 4 day-culture, medium IgM level and cell proliferation were determined by ELISA method and WST-8 method for mitochondrial dehydrogenase activity, respectively. Results showed that PWM-induced IgM production was dose-dependently suppressed by cyclosporin A, a typical immunosuppressor, with more susceptible inhibition of cell proliferation. On the contrary, it was increased by lead nitrate, an immunoenhancer, around 100 µM with little change in the cell proliferation. Moreover some estrogen-related compounds such as estradiol, ethynylestradiol, diethylstilbestrol and bisphenol A dissolved in dimethyl sulfoxide were applied to the assay system. Those below 1 µM affect neither the IgM production nor the cell proliferation in spleen cell cultures irrespective of mouse sex. Further for detecting active metabolites, the preincubation of a chemical with S9 mix was coupled with the assay system. The availability of the procedure was confirmed by inhibitory effect of cyclophosphamide after preincubation with S9 mix, which had no effect without S9 mix. Thus the newly developed in vitro IgM production system by mouse spleen cells is effective for evaluating toxic or modulating effects of chemicals on antibody production.

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“…transport. Thus, the zinc supplement may protect humans against the cadmium-induced immunotoxicity Grazia-Cifone et al 1989;Borella and Giardino 1991;Daum et al 1993). At present, we did not examine the effect of cadmium exposure on Ca 2?…”

Section: Characteristics Of Membrane CD 2? Pathwaymentioning

confidence: 84%

“…Cadmium is an environmental pollutant with a variety of immunotoxic actions Grazia-Cifone et al 1989;Borella and Giardino 1991;Daum et al 1993). Cadmium-induced apoptosis of lymphocytes is one of common features in the immunotoxicity of cadmium (El Azzouzi et al 1994;Tsangaris and Tzortzatou-Stathopoulou 1998;Kim et al 2000;Fujimaki et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Some characteristics of membrane Cd2+ transport in rat thymocytes: an analysis using Fluo-3

et al. 2011

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Although cadmium-induced apoptosis of lymphocytes is one of common features in the immunotoxicity of cadmium, the membrane pathway for intracellular cadmium accumulation is not fully elucidated. To characterize membrane Cd(2+) transport of rat thymocytes, the change in intracellular Cd(2+) concentration under various conditions was examined by the use of Fluo-3, a fluorescent probe for monitoring the change in intracellular concentration of divalent metal cations. The membrane Cd(2+) transport was estimated by the augmentation of Fluo-3 fluorescence induced by bath application of CdCl(2). Lowering temperature strongly suppressed the augmentation of Fluo-3 fluorescence by CdCl(2), suggesting that the metabolic process can be involved in membrane Cd(2+) transport. External acidification (decreasing pH) and membrane depolarization by adding KCl attenuated the augmentation, indicating the requirement of electrochemical driving force for membrane Cd(2+) transport into the cells. Bath application of CaCl(2) and ZnCl(2) equally decreased the augmentation, suggesting their competition with Cd(2+) at the membrane transport. The augmentation by CdCl(2) was lesser in the cells treated with N-ethylmaleimide inducing chemical depletion of cellular thiols. The result suggests the contribution of sulfhydryl groups to membrane Cd(2+) transport. Taken together, it is suggested that the cells possess a temperature-sensitive membrane Cd(2+) pathway, driven by electrochemical gradient of Cd(2+) and transmembrane potential, with competitive binding site. Based on the characteristics described above, it is unlikely that the membrane Cd(2+) transport in rat thymocytes is attributed to a single transport system although it has characteristics that are similar to those of divalent cation transporter 1.

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Lead and cadmium at very low doses affect in vitro immune response of human lymphocytes

Cited by 47 publications

References 30 publications

Neuroimmunotoxicology: Humoral Assessment of Neurotoxicity and Autoimmune Mechanisms

Neuroimmunotoxicology: Humoral Assessment of Neurotoxicity and Autoimmune Mechanisms

A Simple Bioassay for Evaluating Immunotoxic Properties of Chemicals by Use of in Vitro Antibody Production System.

Some characteristics of membrane Cd2+ transport in rat thymocytes: an analysis using Fluo-3

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