| TI:
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Title
Immune Modulation by Cadmium and Lead in the Acute
Reporter Antigen-Popliteal Lymph Node Assay
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| AU:
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Author
Carey, John B; Allshire, Ashley; van Pelt, Frank N
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| AF:
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Author Affiliation
Department of Pharmacology and Therapeutics,
University College Cork, Cork, Ireland
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| SO:
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Source
Toxicological Sciences [Toxicol. Sci.]. Vol. 91,
no. 1, pp. 113-122. May 2006. |
| IS:
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ISSN
1096-6080 |
| DE:
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Descriptors
Metals; Hypersensitivity; Lymphocytes T; Lymph
nodes; Immunoglobulin G; Lead; Adjuvants; Cadmium;
Autoimmunity; Immunotoxicity; Toxins; Mercury;
Lymphocytes B; Immunomodulation; Heavy metals
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| AB:
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Abstract
Immune modulation by heavy metals may cause
serious adverse health effects in humans, although
the mechanisms involved are not well understood.
Both cadmium and lead are important environmental
and occupational toxins. Therefore, in the current
study, the costimulatory/adjuvant effects and the
T-cell-activating potential of these metals (i.e.,
CdCl sub(2) and PbCl sub(2)), are examined. These
immune-modulating properties are critical in the
development of conditions such as allergy,
hypersensitivity, and autoimmunity. Using the
direct popliteal lymph node assay (PLNA) and
reporter antigen-popliteal lymph node assay (RA-PLNA)
both metals were examined individually for
immunotoxicity. Mercury (i.e., HgCl sub(2)) was
included for comparative purposes as its effects
in the RA-PLNA are well documented. Seven days
following a single footpad injection containing
metal and/or RA (trinitrophenyl-ovalbumin [TNP-OVA]
or TNP-Ficoll), BALB/c mice were sacrificed and
the popliteal lymph nodes (PLNs) removed. PLN
cellularity, TNP-specific antibody-secreting cells
(ASCs), and lymphocyte subsets were assessed. All
three metals strongly stimulated T- and B-cell
proliferation and ASC production following
coinjection with the RA TNP-OVA. In each case, ASC
production was skewed towards the IgG sub(1)
isotype. In addition, all three metals induced IgG
production to TNP-Ficoll (although relatively
weakly in the case of Cd). These results show that
each of these metals can provide adjuvant signals
to promote lymphocyte proliferation and enhance
adaptive immune responses to unrelated antigens.
Skewing of immune responses towards T helper type
2 responses suggests that each of these metals can
enhance allergic and hypersensitivity reactions to
environmental antigens. Furthermore, the induction
of IgG responses to TNP-Ficoll, a
T-cell-independent antigen, indicates that each of
these metals can activate neoantigen-specific T
cells. T-cell activation by metals can lead to
metal hypersensitivity and has been implicated in
the development of autoimmunity. This is the first
report of immune modulation by CdCl sub(2) and
PbCl sub(2) in the RA-PLNA. |
| LA:
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Language
English |
| SL:
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Summary Language
English |
| PY:
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Publication Year
2006 |
| PD:
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Publication Date
200605 |
| PT:
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Publication Type
Journal Article |
| PB:
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Publisher
Oxford University Press, Oxford Journals, Great
Clarendon Street Oxford OX2 6DP UK,
|
| CL:
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Classification
X 24222 Analytical procedures |
| UD:
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Update
200604 |
| SF:
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Subfile
Toxicology Abstracts |
| AN:
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Accession Number
6753274 |
| PG:
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Journal Pages
113-122 |
| JV:
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Journal Volume
91 |
| JI:
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Journal Issue
1 |
