Skip Navigation



ToxSci Advance Access published online on July 26, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm188
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
99/2/512    most recent
kfm188v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by McCabe, M.
Right arrow Articles by Rosenspire, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McCabe, M., Jr
Right arrow Articles by Rosenspire, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 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

Low and Non-Toxic Inorganic Mercury Burdens Attenuate BCR-Mediated Signal Transduction

MJ McCabe, Jr*, MD Laiosa*, L Li{dagger}, SL Menard{dagger}, RR Mattingly{ddagger} and AJ Rosenspire{dagger},§

* Department of Environmental Medicine, University of Rochester, Rochester NY {dagger} Department of Immunology and Microbiology, Wayne State University, Detroit, MI {ddagger} Department of Pharmacology, Wayne State University, Detroit, MI

§ Address correspondence and reprint requests to Allen J. Rosenspire, Department of Immunology and Microbiology, 7374 Scott Hall, Wayne State University School of Medicine, Detroit, MI 48201, E-mail: arosenspire{at}wayne.edu

Received May 18, 2007; revision received July 14, 2007; accepted July 18, 2007


  Abstract

The ubiquitous environmental heavy metal contaminant mercury (Hg) is a potent immunomodulator that has been implicated as a factor contributing to autoimmune disease. However, the mechanism(s) whereby Hg initiates or perpetuates autoimmune responses, especially at the biochemical/molecular level, remain poorly understood. Recent work has established a relationship between impaired B Cell Receptor (BCR) signal strength and autoimmune disease. In previous studies we have shown that in mouse WEHI-231 B cells, non-cytotoxic concentrations of inorganic mercury (Hg+2) interfered with BCR-mediated growth control, suggesting that BCR signal strength was impaired by Hg+2. ERK 1,2 MAPK is responsible for the activation of several transcription factors in B cells. Phosphorylation of ERK serves as an essential node of signal integration for the BCR. Thus, the magnitude of ERK activation serves as an operational metric for BCR signal strength. Using Western blotting and phosphospecific flow cytometry, we now show that the kinetics and magnitude of BCR mediated activation of ERK MAP kinase are markedly attenuated in WEHI-231 cells and splenic B cells that have been exposed to low and non-toxic burdens of Hg+2. However, Hg+2 does not seem to act directly on ERK MAP kinase but rather on an upstream element or elements of the BCR signal transduction pathway, above the level of the key protein tyrosine kinase Syk. Our data suggest that the site of action of Hg+2 may very well be localized on the plasma membrane. These findings support a connection between Hg+2 and attenuated BCR signal strength in the etiology of autoimmune disease.

Key Words: Mercury; B Cell Receptor; ERK, Syk.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Am. J. Respir. Cell Mol. Bio.Home page
S.-R. Yang, H. Yao, S. Rajendrasozhan, S. Chung, I. Edirisinghe, S. Valvo, G. Fromm, M. J. McCabe Jr., P. J. Sime, R. P. Phipps, et al.
RelB Is Differentially Regulated by I{kappa}B Kinase-{alpha} in B Cells and Mouse Lung by Cigarette Smoke
Am. J. Respir. Cell Mol. Biol., February 1, 2009; 40(2): 147 - 158.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.