Enhancement of ovalbumin-induced antibody production and mucosal mast cell response by mercury.
Food contaminants may contribute to the recent increased incidence of food allergies. We have investigated this hypothesis experimentally. It was our objective to determine whether toxicity to the intestinal tissue by orally applied mercury (Hg) could modulate the immune response to food allergens. Effective mechanisms were studied with functional immunological and toxicological parameters. Brown Norway rats were immunized intraperitoneally by ovalbumin (OVA). Before oral challenge with OVA, immunized and non-immunized animals were exposed to HgCl2. Immunological responses were measured by enzyme-linked immunosorbent assays [anti-OVA-IgE and-IgG, rat mast cell protease II (RMCPII), interferon-gamma, interleukin-4, lymphocyte proliferation] and by flow cytometry (lymphocyte subpopulations). Toxicity of Hg to the intestinal barrier was determined by measuring viability, DNA damage and induction of glutathione S-transferase in isolated intestinal epithelial cells and lymph node cells, and by measuring permeability, short-circuit current and tissue conductance of the intact intestinal epithelium. A single high oral dose of HgCl2 enhanced the serum concentrations of anti-OVA-IgE and IgG (P < 0.05) and of RMCPII (P < 0.05) in immunized rats. The treatment resulted in a higher number of CD4/CD25+ T cells in the lymph nodes (P < 0.05). The multiple application of low HgCl2 doses (5 x 0.2 mg/kg body weight) only resulted in an elevated RMCPII serum concentration (P < 0.05). Neither treatment schedules impaired proliferation and cytokine production of lymphocytes. In non-immunized rats only minor immunological changes were observed. Oral HgCl2 induced genotoxic damage in lymph node cells and in jejunal epithelial cells (P < 0.05). Moreover, HgCl2 increased the permeability of intestinal epithelial tissue and of Caco-2 monolayers and was genotoxic and cytotoxic to isolated intestinal epithelial cells in vitro. In conclusion, these studies indicate that the food contaminant Hg can stimulate the immune response to OVA in immunized rats. One possible mechanism could be the toxicity of Hg to the intestinal epithelial and the lymph node cells. Whether humans with allergies respond to high oral doses of Hg in a similar way needs to be investigated in further studies.
Watzl
B
B
Institute of Nutritional Physiology, Federal Research Centre for Nutrition, Karlsruhe, Germany.
Abrahamse
S L
SL
Treptow-van Lishaut
S
S
Neudecker
C
C
Hänsch
G M
GM
Rechkemmer
G
G
Pool-Zobel
B L
BL
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D000954:Antigens, Surface / Q000096:biosynthesis; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D019793:Fluorescein / Q000378:metabolism; D005512:Food Hypersensitivity / Q000276:immunology*; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D018928:Immunity, Mucosal / Q000187:drug effects*; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008407:Mast Cells / Q000187:drug effects*; D008628:Mercury / Q000633:toxicity*; D008643:Mesentery / Q000187:drug effects; D010047:Ovalbumin / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012697:Serine Endopeptidases / Q000097:blood
D000954:Antigens, Surface; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin; D005982:Glutathione Transferase; D012697:Serine Endopeptidases; C057818:cytotoxic T lymphocyte-specific serine protease; D008628:Mercury; D019793:Fluorescein