Lead Alters the Immunogenicity of Two Neural Proteins: A Potential Mechanism for the Progression of Lead-Induced Neurotoxicity

Details

• Personal Author:
  El-Fawal HA ; Snyder CA ; Waterman SJ
• Description:
  Some heavy metals have been suspected of playing a role in the pathogenesis of nervous system diseases such as multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease. In these disorders, autoantibodies against neural proteins are evident at some stage of the disease. Lead is known to affect both the immune and nervous systems. Work in our laboratory has shown that lead exposure leads to the production of autoantibodies against neural proteins, including myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP). We hypothesize that lead aggravates neurological disease by enhancing the immunogenicity of nervous system proteins, including MBP and GFAP. To test this hypothesis, lead-altered protein was prepared by incubating MBP or GFAP with lead acetate for 24 hr. On days 0, 14, and 28, mice received inoculations with either saline, native protein, or lead-altered protein. Anti-MBP and anti-GFAP, isotypes IgM and IgG, were measured in sera by ELISA on day 38. Sera of mice treated with lead-altered MBP had statistically higher anti-MBP IgG titers than both control and native MBP-immunized mice. An analogous response was seen in mice immunized with lead-altered GFAP. Supernatants from lectin-stimulated splenocytes were also examined for antibody titers and for interleukin 2 (IL-2) and interleukin 6 (IL-6) levels. A significant increase in IL-6 production was seen in mice immunized with lead-altered MBP but not with lead-altered GFAP. No changes were observed in the IL-2 levels of mice immunized with either lead-altered protein. These results demonstrate that lead does enhance the immunogenicity of two neural system proteins MBP and GFAP and suggests a possible mechanism for an immunologically mediated progression of lead-induced neurotoxicity. In addition, the IL-6 results suggest that lead-altered MBP may induce antibody production through a different immunological mechanism from lead-altered GFAP. [Description provided by NIOSH]
• Subjects:
  Animals Immune System Lead Nervous System Occupational Health Safety
• Keywords:
  Animal Studies Author Keywords: Immunogenicity Immune Reaction Immunological Tests Neural Protein Neurological Diseases Neurological System Neurotoxic Effects Neurotoxicity Neurotoxins Proteins

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• ISSN:
  0091-6765
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  New York ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  102
• Issue:
  12
• NIOSHTIC Number:
  nn:20060063
• Citation:
  Environ Health Perspect 1994 Dec; 102(12):1052-1056
• Contact Point Address:
  C.A. Snyder, New York University Institute of Environmental Medicine, Nelson Institute of Environmental Medicine, Long Meadow Road, Tuxedo, NY 10987 USA
• CAS Registry Number:
  Lead (CAS RN 7439-92-1)
• Federal Fiscal Year:
  1995
• Performing Organization:
  Mount Sinai School of Medicine, New York
• Peer Reviewed:
  True
• Start Date:
  19920701
• Source Full Name:
  Environmental Health Perspectives
• End Date:
  19970630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:190a847a0524c620e78781a30b3b06afd761a1ad721df72074452e6cb2eeac2c0292e579a7fa5768aa1eaa7e3ecad72efde2a50220ad208280bf536c1862f714
• Download URL:
  https://stacks.cdc.gov/view/cdc/224096/cdc_224096_DS1.pdf
• File Type:
  [PDF - 328.70 KB ]