Mercury is a widespread environmental contaminant whose toxic potential to the nervous and immune systems is well known. Surprisingly little is known about its molecular mechanism of action. While high level exposure is no longer common, large segments of the population currently absorb low (-.10 ug/day) levels of mercury as a result of ubiquitous environmental factors, including air, food, water, and dental amalgam. For about 3 percent of the population with no known special risk factors, blood levels of mercury exceed 0.25 uM. 4 percent of the population exceed 0.125 uM mercury in urine, with the highest concentrations reported in individuals with no known special risk factors to be about 1 uM. Preliminary and recently published results from our laboratories support our hypothesis that concentrations of inorganic mercury in the range of 0.1- 1.0 uM may directly impair immune system homeostasis, and contribute to autoimmune disease by interfering with protein tyrosine phosphorylation (PTK)mediated signal transduction, implying that substantial numbers of individuals may unknowingly be at risk. In this proposal it is our objective to critically and comprehensively test our hypothesis in several different cell systems relevant to autoimmune disease. In particular, we will test mercury's ability to interfere with antigen receptor mediated and P1K-dependent signal transduction and proliferative control in established T and B cell lines, as well as in freshly isolated human peripheral blood lymphocytes. We will also examine the effect that low concentrations of mercury have on antigen receptor mediated apoptosis in lymphocytes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES011000-03
Application #
6686382
Study Section
Alcohol and Toxicology Subcommittee 4 (ALTX)
Program Officer
Tinkle, Sally S
Project Start
2002-02-19
Project End
2005-11-30
Budget Start
2003-12-01
Budget End
2004-11-30
Support Year
3
Fiscal Year
2004
Total Cost
$334,175
Indirect Cost
Name
Wayne State University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
001962224
City
Detroit
State
MI
Country
United States
Zip Code
48202
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