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Title: Macrophages are involved in hexachlorobenzene-induced adverse immune effects

Abstract

Hexachlorobenzene (HCB) is a persistent environmental pollutant that causes adverse immune effects in man and rat. The Brown Norway (BN) rat is very susceptible to HCB-induced immunopathology and oral exposure causes inflammatory skin and lung lesions, splenomegaly, lymph node (LN) enlargement, and increased serum levels of IgE and anti-ssDNA IgM. T cells play an important role but do not account for all adverse effects induced by HCB. Macrophages are probably also important and the relationship between macrophages and T cells was further investigated. To eliminate macrophages clodronate-liposomes were used. Furthermore, a kinetic study was performed to obtain insight in the early phase of the HCB-induced immune response. Also, experiments were performed to detect specific memory T cells. Therefore, an adoptive transfer study was performed. Our results indicate that macrophages are indeed involved in HCB-induced skin lesions, lung eosinophilia, and elevation of IgM against ssDNA. Kinetics showed that both skin and lung lesions appeared early after exposure. Moreover, immune effects could not be adaptively transferred. Thus, both macrophages and T cells are involved in HCB-induced immune effects but HCB exposure does not lead to specific T cell sensitization. Presumably, HCB exposure induces macrophage activation, thereby generating adjuvant signals that polyclonally stimulatemore » T cells. Together, these events may lead to the observed immunopathology in BN rats.« less

Authors:
 [1];  [2];  [2];  [2];  [2];  [3];  [4];  [5];  [2]
  1. National Institute for Public Health and the Environment, Laboratory for Toxicology, Pathology and Genetics, Bilthoven, PO Box 1 3720 BA (Netherlands). E-mail: Janine.Ezendam@rivm.nl
  2. Institute for Risk Assessment Sciences (IRAS), Immunotoxicology, Utrecht University, PO Box 80.176, 3508 TD Utrecht (Netherlands)
  3. Faculty of Medicine, Department of Molecular Cell Biology, Free University, PO Box 7057, 1007 MB Amsterdam (Netherlands)
  4. National Institute for Public Health and the Environment, Laboratory for Toxicology, Pathology and Genetics, Bilthoven, PO Box 1 3720 BA (Netherlands)
  5. (Netherlands)
Publication Date:
OSTI Identifier:
20783367
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 209; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2005.03.010; PII: S0041-008X(05)00152-3; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BORON NITRIDES; INFLAMMATION; LIPOSOMES; LUNGS; LYMPH NODES; MACROPHAGES; POLLUTANTS; RATS; SKIN; SPLENOMEGALY

Citation Formats

Ezendam, Janine, Kosterman, Kevin, Spijkerboer, Henneke, Bleumink, Rob, Hassing, Ine, Rooijen, Nico van, Vos, Joseph G., Faculty of Veterinary Medicine, Department of Pathobiology, Utrecht University, PO Box 80.150, 3508 TD Utrecht, and Pieters, Raymond. Macrophages are involved in hexachlorobenzene-induced adverse immune effects. United States: N. p., 2005. Web. doi:10.1016/j.taap.2005.03.010.
Ezendam, Janine, Kosterman, Kevin, Spijkerboer, Henneke, Bleumink, Rob, Hassing, Ine, Rooijen, Nico van, Vos, Joseph G., Faculty of Veterinary Medicine, Department of Pathobiology, Utrecht University, PO Box 80.150, 3508 TD Utrecht, & Pieters, Raymond. Macrophages are involved in hexachlorobenzene-induced adverse immune effects. United States. doi:10.1016/j.taap.2005.03.010.
Ezendam, Janine, Kosterman, Kevin, Spijkerboer, Henneke, Bleumink, Rob, Hassing, Ine, Rooijen, Nico van, Vos, Joseph G., Faculty of Veterinary Medicine, Department of Pathobiology, Utrecht University, PO Box 80.150, 3508 TD Utrecht, and Pieters, Raymond. Tue . "Macrophages are involved in hexachlorobenzene-induced adverse immune effects". United States. doi:10.1016/j.taap.2005.03.010.
@article{osti_20783367,
title = {Macrophages are involved in hexachlorobenzene-induced adverse immune effects},
author = {Ezendam, Janine and Kosterman, Kevin and Spijkerboer, Henneke and Bleumink, Rob and Hassing, Ine and Rooijen, Nico van and Vos, Joseph G. and Faculty of Veterinary Medicine, Department of Pathobiology, Utrecht University, PO Box 80.150, 3508 TD Utrecht and Pieters, Raymond},
abstractNote = {Hexachlorobenzene (HCB) is a persistent environmental pollutant that causes adverse immune effects in man and rat. The Brown Norway (BN) rat is very susceptible to HCB-induced immunopathology and oral exposure causes inflammatory skin and lung lesions, splenomegaly, lymph node (LN) enlargement, and increased serum levels of IgE and anti-ssDNA IgM. T cells play an important role but do not account for all adverse effects induced by HCB. Macrophages are probably also important and the relationship between macrophages and T cells was further investigated. To eliminate macrophages clodronate-liposomes were used. Furthermore, a kinetic study was performed to obtain insight in the early phase of the HCB-induced immune response. Also, experiments were performed to detect specific memory T cells. Therefore, an adoptive transfer study was performed. Our results indicate that macrophages are indeed involved in HCB-induced skin lesions, lung eosinophilia, and elevation of IgM against ssDNA. Kinetics showed that both skin and lung lesions appeared early after exposure. Moreover, immune effects could not be adaptively transferred. Thus, both macrophages and T cells are involved in HCB-induced immune effects but HCB exposure does not lead to specific T cell sensitization. Presumably, HCB exposure induces macrophage activation, thereby generating adjuvant signals that polyclonally stimulate T cells. Together, these events may lead to the observed immunopathology in BN rats.},
doi = {10.1016/j.taap.2005.03.010},
journal = {Toxicology and Applied Pharmacology},
number = 1,
volume = 209,
place = {United States},
year = {Tue Nov 15 00:00:00 EST 2005},
month = {Tue Nov 15 00:00:00 EST 2005}
}
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