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. CONCLUSION: 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.
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. CONCLUSION: 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.
Authors: Zun Liu; Shikha Bhattacharyya; Bo Ning; Terumi Midoro-Horiuti; Edmund W Czerwinski; Randall M Goldblum; Andrew Mort; Christopher M Kearney Journal: Int Arch Allergy Immunol Date: 2010-06-17 Impact factor: 2.749
Authors: Masafumi Zaitsu; Shin-Ichiro Narita; K Chad Lambert; James J Grady; D Mark Estes; Edward M Curran; Edward G Brooks; Cheryl S Watson; Randall M Goldblum; Terumi Midoro-Horiuti Journal: Mol Immunol Date: 2006-11-03 Impact factor: 4.407
Authors: Shin-ichiro Narita; Randall M Goldblum; Cheryl S Watson; Edward G Brooks; D Mark Estes; Edward M Curran; Terumi Midoro-Horiuti Journal: Environ Health Perspect Date: 2007-01 Impact factor: 9.031