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ToxSci Advance Access originally published online on March 12, 2007
Toxicological Sciences 2007 97(2):364-374; doi:10.1093/toxsci/kfm048
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© The Author 2007. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

3,4-Dichloropropionaniline Suppresses Normal Macrophage Function

Irina V. Ustyugova*,3, Laura L. Frost*,2,3, Knox VanDyke{dagger}, Kathleen M. Brundage*,{ddagger}, Rosana Schafer*,{ddagger} and John B. Barnett*,{ddagger},1

* Department of Microbiology, Immunology and Cell Biology {dagger} Department of Biochemistry and Molecular Pharmacology {ddagger} Center for Immunopathology and Microbial Pathogenesis, West Virginia University, PO Box 9177, Morgantown, West Virginia 26506-9177

1 To whom correspondence should be addressed. Fax: (304) 293-7823. E-mail: jbarnett{at}hsc.wvu.edu.

Received December 14, 2006; accepted March 5, 2007


  Abstract

Macrophages are a critical part of the innate immune response and natural surveillance mechanisms. As such, proper macrophage function is crucial for engulfing bacterial pathogens through phagocytosis and destroying them by generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). The production of a number of cytokines by macrophages, such as tumor necrosis factor-{alpha} (TNF-{alpha}), interleukin (IL)-1ß, and IL-6, plays an important role in the initiation of the acquired immune response creating an inflammatory environment favorable for fighting a bacterial infection. 3,4-Dichloropropionaniline (DCPA) suppresses several inflammatory parameters, including TNF-{alpha} production through a mechanism where nuclear factor-{kappa}B (NF-{kappa}B)–DNA binding is inhibited but not entirely abrogated. The goal of the present study was to evaluate the effects of DCPA on the inflammatory mediators of macrophages, including ROS and RNS in both murine peritoneal exudate cells and the human monocytic cell line, THP-1. The ability to perform phagocytosis and directly kill Listeria monocytogenes was also assessed. The results indicate that DCPA decreases the ability of both types of macrophages to phagocytize beads and generate both types of reactive species, which was correlated with a decrement in listericidal activity. These results demonstrate that DCPA has profound effects on macrophage function and provide insight into the potential mechanisms of immunosuppression by DCPA.

Key Words: bactericidal; phagocytosis; Listeria monocytogenes; dichloropropionaniline; macrophage; THP-1 cell line.

2 Present address: Department of Natural Sciences and Engineering Technology, Point Park University, Pittsburgh, PA 15222.

3 These authors contributed equally to this study.


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[Abstract] [Full Text] [PDF]


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