Murine mast cells exposed to mercuric chloride release granule-associated N-acetyl-beta-D-hexosaminidase and secrete IL-4 and TNF-alpha.
BACKGROUND
Mast cells, by virtue of their location within the skin, respiratory tract, and gastrointestinal system, are considered as potential targets for environmental agents with immunotoxic effects. Mercuric chloride (HgCl2), is a xenobiotic, which induces autoimmune glomerulonephritis and stimulates polyclonal IgE production.


OBJECTIVE
We sought to determine the ability of HgCl2 to degranulate murine mast cells and promote cytokine secretion and whether this was an active biologic process.


METHODS
Bone marrow-derived murine mast cells were exposed to HgCl2, and the release of N-acetyl-beta-D-hexosaminidase and secretion of IL-4 and TNF-alpha were measured.


RESULTS
HgCl2 was found to directly activate murine mast cells to release the granule-associated enzyme N-acetyl-beta-D-hexosaminidase and to secrete the proinflammatory cytokines IL-4 and TNF-alpha. Cytokine secretion occurred hours after exposure to HgCl2 and required transcription and protein synthesis. The secretion of cytokines mediated by HgCl2 was additive to that which followed FcepsilonRI-induced mast cell activation. The IL-4 secretion by mast cells occurred at concentrations of HgCl2 (10(-6) mol/L to 10(-5) mol/L) comparable with those required to induce upregulation of IgE production in experimental animals.


CONCLUSIONS
These findings demonstrate that HgCl2 will directly activate mast cells, which is followed by degranulation and IL-4 and TNF-alpha synthesis and secretion. These findings are consistent with recognition of HgCl2 as a biologically important environmentally derived immunotoxic agent for mast cells.
Dastych
J
J
Department of Biogenic Amines, Polish Academy of Sciences, Lodz, Poland.
Walczak-Drzewiecka
A
A
Wyczolkowska
J
J
Metcalfe
D D
DD
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D015550:Cell Degranulation / Q000187:drug effects; D002478:Cells, Cultured; D015847:Interleukin-4 / Q000378:metabolism*; D008407:Mast Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D008627:Mercuric Chloride / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D008627:Mercuric Chloride; D001619:beta-N-Acetylhexosaminidases