PMID- 12426151
OWN - NLM
STAT- MEDLINE
DCOM- 20021224
LR  - 20181113
IS  - 0091-6765 (Print)
IS  - 0091-6765 (Linking)
VI  - 110 Suppl 5
IP  - Suppl 5
DP  - 2002 Oct
TI  - Mercury-induced autoimmunity in mice.
PG  - 877-81
AB  - We have studied the effect of gender, genetics, and toxicokinetics on immune 
      parameters in mercury-induced autoimmunity in mice. Data strongly suggest that 
      the mechanism for mercury-induced autoimmunity involves modification of the 
      autoantigen fibrillarin by mercury followed by a T-cell-dependent immune response 
      driven by the modified fibrillarin. Mice with different H-2 haplotypes were 
      treated with (203)HgCl(2) in a dose of 0.5-16 mg Hg/L drinking water for 10 
      weeks. Whole-body accumulation and renal accumulation of mercury were assessed. 
      Serum antinuclear antibodies were used to evaluate the autoimmune response, and 
      serum immunoglobulin E (IgE) to study effects on T-helper cells of type 2. 
      Strains with a susceptible H-2 haplotype developed autoantibodies to the 
      nucleolar protein fibrillarin (AFA) in a dose-dependent pattern within 2 weeks. 
      The substantially lower whole-body and organ mercury level needed to induce AFA 
      in the susceptible A.SW strain compared with the H-2 congenic B10.S strain 
      demonstrates that genetic factors outside the H-2 region modify the autoimmune 
      response. Mouse strains without the susceptible haplotype did not develop any 
      autoimmune reaction irrespective of dose and organ deposition of mercury. In 
      susceptible mouse strains, males and females had different thresholds for 
      induction of autoimmune reactions. In susceptible strains, serum IgE increased 
      dose dependently and reached a maximum after 1-2.5 weeks. A susceptible H-2 
      haplotype is therefore a prerequisite for the autoimmune response. Mercury 
      exposure will modulate the response, qualitatively through the existence of 
      dose-related thresholds for autoimmune response and quantitatively as increasing 
      doses cause increasing autoimmune response. Further, gender and non-H-2 genes 
      modulate both the induction and subsequent development of AFA. Induction of IgE 
      seems not to be mechanistically linked to the AFA response.
FAU - Nielsen, Jesper Bo
AU  - Nielsen JB
AD  - Environmental Medicine, University of Southern Denmark, Winslowparken 17, DK-5000 
      Odense C, Denmark. jbnielsen@health.sdu.dk
FAU - Hultman, Per
AU  - Hultman P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Environ Health Perspect
JT  - Environmental health perspectives
JID - 0330411
RN  - 0 (Chromosomal Proteins, Non-Histone)
RN  - 0 (Environmental Pollutants)
RN  - 0 (fibrillarin)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - FXS1BY2PGL (Mercury)
SB  - IM
MH  - Animals
MH  - Autoimmune Diseases/*chemically induced/genetics/*veterinary
MH  - Chromosomal Proteins, Non-Histone/*biosynthesis/drug effects
MH  - Disease Models, Animal
MH  - Environmental Pollutants/*adverse effects/*immunology
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Haplotypes
MH  - Immunoglobulin E/analysis/*biosynthesis
MH  - Kinetics
MH  - Male
MH  - Mercury/*adverse effects/*immunology
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Sex Factors
PMC - PMC1241265
EDAT- 2002/11/12 04:00
MHDA- 2002/12/27 04:00
PMCR- 2002/10/01
CRDT- 2002/11/12 04:00
PHST- 2002/11/12 04:00 [pubmed]
PHST- 2002/12/27 04:00 [medline]
PHST- 2002/11/12 04:00 [entrez]
PHST- 2002/10/01 00:00 [pmc-release]
AID - sc271_5_1835 [pii]
AID - 10.1289/ehp.02110s5877 [doi]
PST - ppublish
SO  - Environ Health Perspect. 2002 Oct;110 Suppl 5(Suppl 5):877-81. doi: 
      10.1289/ehp.02110s5877.