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, respir atory tract, and gastrointestinal system, are considered as potential targe ts for environmental agents with immunotoxic effects, Mercuric chloride (Hg Cl2), is a xenobiotic, which induces autoimmune glomerulonephritis and stim ulates polyclonal IgE production. Objective: We sought to determine the ability of HgCl2 to degranulate murin e 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 t he 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 occur red hours after exposure to HgCl2 and required transcription and protein sy nthesis. The secretion of cytokines mediated by HgCl2 was additive to that which followed Fc epsilon RI-induced mast cell activation. The IL-4 secreti on 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 produ ction in experimental animals. Conclusion: These findings demonstrate that HgCl2 will directly activate ma st cells, which is followed by degranulation and IL-4 and TNF-alpha synthes is and secretion. These findings are consistent with recognition of HgCl2 a s a biologically important environmentally derived immunotoxic agent for ma st cells.