Hexachlorobenzene-Induced Stimulation of the Humoral Immune Response in Rats

Vos, J.G.; Logten, M.J. van; Kreeftenberg, J.G.; Kruizinga, W.

doi:10.1111/j.1749-6632.1979.tb13175.x

Cited by 41 publications

(20 citation statements)

References 9 publications

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“…Furthermore, HCB increased gene expression of CD52 or B7 antigen, a marker present on antigen-presenting cells, such as B cells and monocytes. This is in line with previous studies that have shown a stronger increase of monocytes and granulocytes in blood after HCB exposure, resulting in relatively fewer lymphocytes (Schulte et al 2002;Vos et al 1979). In kidney we observed an increased expression of OX 45 (homolog to CD2), a membrane protein involved in the binding to LFA-3, important in adhesion of T cells to other cell types and in T-cell activation.…”

Section: T and B Cells And Major Histocompatibility Complex II Expressupporting

confidence: 82%

Toxicogenomics of Subchronic Hexachlorobenzene Exposure in Brown Norway Rats

Ezendam¹,

Staedtler²,

Pennings³

et al. 2004

Environ. Health Perspect.

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) for performing the radioimmunoassay to determine antiacetylcholine receptor antibodies, and we thank B. Baumann (RIVM, Bilthoven, the Netherlands) for measuring the dioxin-like contamination of HCB.The authors declare they have no competing financial interests.Received 13 Hexachlorobenzene (HCB) is a persistent environmental pollutant with toxic effects in man and rat. Reported adverse effects are hepatic porphyria, neurotoxicity, and adverse effects on the reproductive and immune system. To obtain more insight into HCB-induced mechanisms of toxicity, we studied gene expression levels using DNA microarrays. For 4 weeks, Brown Norway rats were fed a diet supplemented with 0, 150, or 450 mg HCB/kg. Spleen, mesenteric lymph nodes (MLN), thymus, blood, liver, and kidney were collected and analyzed using the Affymetrix rat RGU-34A GeneChip microarray. Most significant (p < 0.001) changes, compared to the control group, occurred in spleen, followed by liver, kidney, blood, and MLN, but only a few genes were affected in thymus. This was to be expected, as the thymus is not a target organ of HCB. Transcriptome profiles confirmed known effects of HCB such as stimulatory effects on the immune system and induction of enzymes involved in drug metabolism, porphyria, and the reproductive system. In line with previous histopathological findings were increased transcript levels of markers for granulocytes and macrophages. New findings include the upregulation of genes encoding proinflammatory cytokines, antioxidants, acute phase proteins, mast cell markers, complements, chemokines, and cell adhesion molecules. Generally, gene expression data provide evidence that HCB induces a systemic inflammatory response, accompanied by oxidative stress and an acute phase response. In conclusion, this study confirms previously observed (immuno)toxicological effects of HCB but also reveals several new and mechanistically relevant gene products. Thus, transcriptome profiles can be used as markers for several of the processes that occur after HCB exposure.

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Section: T and B Cells And Major Histocompatibility Complex II Expressupporting

confidence: 82%

Toxicogenomics of Subchronic Hexachlorobenzene Exposure in Brown Norway Rats

Ezendam¹,

Staedtler²,

Pennings³

et al. 2004

Environ. Health Perspect.

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“…In these infants a condition called Pembe Yara has been described, characterized by rose-red skin lesions on arms and legs, enlarged livers, diarrhea, and fever. There was a high mortality (> 95%) among young children who were exposed to HCB via the placenta or maternal milk (51,53,54 (59)(60)(61)(62). Histopathologic examination of the spleen and lymph nodes showed increased extramedullary hemopoiesis in the red pulp and hyperplasia of B lymphocytes in marginal zones and follicles of the spleen as well as an increase in high endothelial venules in the lymph nodes (49,50,59).…”

Section: Accidental Human Poisoning In Turkeymentioning

confidence: 99%

“…There was a high mortality (> 95%) among young children who were exposed to HCB via the placenta or maternal milk (51,53,54 (59)(60)(61)(62). Histopathologic examination of the spleen and lymph nodes showed increased extramedullary hemopoiesis in the red pulp and hyperplasia of B lymphocytes in marginal zones and follicles of the spleen as well as an increase in high endothelial venules in the lymph nodes (49,50,59). Functional assessment of the immune system showed no significant effect of HCB on the phagocytizing and killing capacity of macrophages as shown by Listeria monocytogenes mortality assay and clearance of colloidal carbon.…”

Section: Accidental Human Poisoning In Turkeymentioning

confidence: 99%

The role of the immune system in hexachlorobenzene-induced toxicity.

Michielsen

Loveren

Vos

1999

Environ Health Perspect

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Hexachlorobenzene (HCB) is a persistent environmental pollutant. The toxicity of HCB has been extensively studied after an accidental human poisoning in Turkey and more recently it has been shown that HCB has immunotoxic properties in laboratory animals and probably also in man. Oral exposure of rats to HCB showed stimulatory effects on spleen and lymph node weights and histology, increased serum IgM levels, and an enhancement of several parameters of immune function. Moreover, more recent studies indicate that HCB-induced effects in the rat may be related to autoimmunity. In Wistar rats exposed to HCB, IgM antibodies against several autoantigens were elevated; in the Lewis rat, HCB differently modulated two experimental models of autoimmune disease. Oral exposure of rats to HCB induces skin and lung pathology in the rat. Recently several studies have been conducted to investigate whether these skin and lung lesions can be related to HCB-induced immunomodulation, and these studies will be discussed in this review. HCB-induced skin and lung lesions probably have a different etiology; pronounced strain differences and correlation of skin lesions with immune parameters suggest a specific involvement of the immune system in HCB-induced skin lesions. The induction of lung lesions by HCB was thymus independent. Thymus-dependent T cells were not likely to be required for the induction of skin lesions, although T cells enhanced the rate of induction and the progression of the skin lesions. No deposition of autoantibodies was observed in nonlesional or lesional skin of HCB-treated rats. Therefore, we concluded that it is unlikely that the mechanism by which most allergic or autoimmunogenic chemicals work, i.e., by binding to macromolecules of the body and subsequent T-and B-cell activation, is involved in the HCB-induced immunopathology in the rat. Such a thymus-independent immunopathology is remarkable, as HCB strongly modulates T-cell-mediated immune parameters. This points at a very complex mechanism and possible involvement of multiple factors in the immunopathology of HCB.

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“…Histopathologically, the spleen shows hyperplasia of B-lymphocytes in marginal zones and follicles. Lymph nodes are activated as shown by the appearance of secondary follicles and an increase in the number of high endothelial venules in T-dependent areas 23 . High endothelial-like venules are also induced in the lung (Fig.…”

Section: Hexachlorobenzene (Hcb)mentioning

confidence: 99%

“…The developing immune system appears to be particularly vulnerable, as observed in two dietary studies investigating the prenatal and postnatal toxicity of HCB. In the first study, Wistar rats received 0, 50 or 150 mg/kg HCB starting at days 1-3 of pregnancy 23 . Clear immunostimulatory effects were noted in the 50 mg/kg group, therefore a second prenatal and …”

Section: Hexachlorobenzene (Hcb)mentioning

confidence: 99%

Chemically-Induced Immunopathology and Immune Functional Changes

Vos

Kuper²

2004

J Toxicol Pathol

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Toxicological pathology of lymphoid organs plays an important role in the risk assessment process of immunotoxicants. Identification of chemicals that have the potential to cause injury to the immune system is of considerable public health significance because of the role of the immune system in infectious diseases, hypersensitivity reactions and autoimmune diseases. In assessing immunotoxicity, a two-tier testing system is usually employed in rodents in which the first tier is a general screen for (immuno)toxicity including enhanced histopathology of lymphoid organs and the second tier consists of more specific immune function studies including host resistance tests or mechanistic studies. Studies with the potent immunotoxicants TCDD, TBTO, HCB, azathioprine and cyclosporin A are discussed, which provide data correlating histopathology with immune function changes. This is followed by a discussion of the outcomes of enhanced histopathology investigation in the interlaboratory validation studies with azathioprine, cyclosporin A and HCB in the rat, as well as the results of a recent evaluation of enhanced histopathology in the mouse as an indicator of immunotoxicity. From these studies, that have been the basis for a number of regulatory activities, the following conclusions can be drawn: i) the consistency between histopathology and functional tests, ii) the complimentary information of pathology and immunology observations, and iii) the dependence on standardised protocols and trained toxicologic pathologists to accurately identify and grade microscopical changes in lymphoid organs and tissues. (J Toxicol Pathol 2004; 17: 137-146)

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Hexachlorobenzene-Induced Stimulation of the Humoral Immune Response in Rats

Cited by 41 publications

References 9 publications

Toxicogenomics of Subchronic Hexachlorobenzene Exposure in Brown Norway Rats

Toxicogenomics of Subchronic Hexachlorobenzene Exposure in Brown Norway Rats

The role of the immune system in hexachlorobenzene-induced toxicity.

Chemically-Induced Immunopathology and Immune Functional Changes

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