Mercuric chloride enhances immunoglobulin E-dependent mediator release from human basophils.
Mercuric chloride (HgCl2) is an industrial agent known to cause autoimmune disorders and induce IgE synthesis, which plays a crucial role in the manifestation of allergic diseases. In rodents, the immunomodulatory effects of HgCl2 have been shown to involve the enhancement of mast cell-derived IL-4 secretion, which facilitates both Th2-lymphocyte development and IgE production. In humans, rapid allergen-dependent release of IL-4 and the related cytokine IL-13 from histamine-containing cells occurs primarily in basophils, along with other proinflammatory mediators such as histamine and LTC4. In this study, we therefore investigated the effects of HgCl2 on the release of the above basophil mediators, either due to the compound alone or in conjunction with IgE-dependent stimulation. HgCl2 (10(-9) to 10(-6) M) did not induce mediator secretion alone but significantly enhanced the release of histamine, LTC4, IL-4, and IL-13 caused by anti-IgE. Higher concentrations of HgCl2 (10(-5) to 10(-3) M) strikingly reduced cell viability; however, toxicity varied depending on cell density and incubation time. Removal of HgCl2 following a short incubation with basophils did not reverse the potentiating effects on basophil mediator secretion to anti-IgE and the concentration of free mercury in the supernatants significantly diminished by up to 20% after incubation with the cells, indicating irreversible Hg binding to cells. By upregulating IgE-dependent human basophil mediator release, our results clearly indicate that HgCl2 potentially exacerbates allergic disorders and promotes a Th2-cytokine profile.
Strenzke
N
N
Department of Dermatology, Medical University of Lübeck, Lübeck, Germany.
Grabbe
J
J
Plath
K E
KE
Rohwer
J
J
Wolff
H H
HH
Gibbs
B F
BF
D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001491:Basophils / Q000187:drug effects* / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D018793:Interleukin-13 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D017997:Leukotriene C4 / Q000032:analysis; D008627:Mercuric Chloride / Q000494:pharmacology* / Q000633:toxicity
D000888:Antibodies, Anti-Idiotypic; D018793:Interleukin-13; C026408:anti-IgE antibodies; D015847:Interleukin-4; D017997:Leukotriene C4; D007073:Immunoglobulin E; D008627:Mercuric Chloride