| Low-dose synergistic immunosuppression of T-dependent antibody responses by polycyclic aromatic hydrocarbons and arsenic in C57BL/6J murine spleen cells. | |
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MedLine Citation:
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PMID: 20353797 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Polycyclic aromatic hydrocarbons (PAHs) and arsenic are both environmental agents that are known to have significant immunotoxicity. Previous studies have shown that PAH exposure of spleen cells in vitro produces significant immune suppression of humoral immunity, especially when P450 activation products are examined. Exposure to arsenic, particularly sodium arsenite, has also been found to be suppressive to antibody responses in vitro and in vivo. The purpose of the present studies was to examine the immunotoxicity of PAHs and arsenite following coexposures with the theory being that the agents may exert synergistic actions, which might be based on their different mechanisms of action. Spleen cells were isolated from male C57BL/6J wild-type mice and treated with PAHs and/or arsenic (arsenite or arsenate). Immunotoxicity assays were used to assess the T-dependent antibody response (TDAR) to sheep red blood cells (SRBCs), measured by a direct plaque-forming cell (PFC) assay. Cell viability was measured by trypan blue staining. Spleen cell viability was not altered following 4 days of PAH and/or arsenic treatment. However, the TDAR demonstrated suppression by both PAHs and arsenic in a concentration-dependent manner. p53 was also induced by NaAsO(2) (As(3)(+)) and PAHs alone or in combination. The PAHs and their metabolites investigated included benzo[a]pyrene (BaP), BaP-7,8-diol, BaP-7,8-diol-9,10-epoxide (BPDE), 7,12-dimethylbenz[a]anthracene (DMBA), DMBA-3,4-diol, dibenzo[a,l]pyrene (DB[a,l]P). PAH metabolites were found to be more potent than parent compounds in producing immunosuppression and inducing p53 expression. Interestingly, DB[a,l]P, a potent carcinogenic PAH not previously characterized for immunotoxicity, was also found to be strongly immunosuppressive. Arsenite (NaAsO(2), As(3)(+)) was found to produce immunosuppression at concentrations as low as 0.5 microM and was immunosuppressive at a 10-fold lower concentration than sodium arsenate (Na(2)HAsO(4), As(5)(+)). Coexposure of spleen cell cultures to PAHs and As(3)(+), both at individual low-effect concentrations, was found to produce profound suppression of the TDAR demonstrating synergy between these two chemical classes of agents. |
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Authors:
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Qian Li; Fredine T Lauer; Ke Jian Liu; Laurie G Hudson; Scott W Burchiel |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-28 |
Journal Detail:
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Title: Toxicology and applied pharmacology Volume: 245 ISSN: 1096-0333 ISO Abbreviation: Toxicol. Appl. Pharmacol. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-21 Completed Date: 2010-06-03 Revised Date: 2013-03-05 |
Medline Journal Info:
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Nlm Unique ID: 0416575 Medline TA: Toxicol Appl Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 344-51 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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The University of New Mexico College of Pharmacy, Department of Pharmaceutical Sciences, Albuquerque, NM, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibody Formation / drug effects Arsenates / toxicity* Arsenites / toxicity* Blotting, Western Cell Survival / drug effects Cells, Cultured Dose-Response Relationship, Drug Drug Synergism Environmental Pollutants / toxicity* Erythrocytes / immunology Immunity, Humoral / drug effects* Immunosuppressive Agents / toxicity* Male Mice Mice, Inbred C57BL Polycyclic Hydrocarbons, Aromatic / toxicity* Sheep Sodium Compounds / toxicity* Spleen / drug effects*, immunology, metabolism T-Lymphocytes / drug effects*, immunology, metabolism Time Factors Tumor Suppressor Protein p53 / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01 ES005495/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Arsenates; 0/Arsenites; 0/Environmental Pollutants; 0/Immunosuppressive Agents; 0/Polycyclic Hydrocarbons, Aromatic; 0/Sodium Compounds; 0/Tumor Suppressor Protein p53; 48OVY2OC72/sodium arsenite; 7631-89-2/sodium arsenate |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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