title: Mercury induces inflammatory mediator release from human mast cells.
abstract: BACKGROUND
  Mercury is known to be neurotoxic, but its effects on the immune system are less well known. Mast cells are involved in allergic reactions, but also in innate and acquired immunity, as well as in inflammation. Many patients with Autism Spectrum Disorders (ASD) have "allergic" symptoms; moreover, the prevalence of ASD in patients with mastocytosis, characterized by numerous hyperactive mast cells in most tissues, is 10-fold higher than the general population suggesting mast cell involvement. We, therefore, investigated the effect of mercuric chloride (HgCl2) on human mast cell activation.
  
  
  METHODS
  Human leukemic cultured LAD2 mast cells and normal human umbilical cord blood-derived cultured mast cells (hCBMCs) were stimulated by HgCl2 (0.1-10 microM) for either 10 min for beta-hexosaminidase release or 24 hr for measuring vascular endothelial growth factor (VEGF) and IL-6 release by ELISA.
  
  
  RESULTS
  HgCl2 induced a 2-fold increase in beta-hexosaminidase release, and also significant VEGF release at 0.1 and 1 microM (311 +/- 32 pg/106 cells and 443 +/- 143 pg/106 cells, respectively) from LAD2 mast cells compared to control cells (227 +/- 17 pg/106 cells, n = 5, p < 0.05). Addition of HgCl2 (0.1 microM) to the proinflammatory neuropeptide substance P (SP, 0.1 microM) had synergestic action in inducing VEGF from LAD2 mast cells. HgCl2 also stimulated significant VEGF release (360 +/- 100 pg/106 cells at 1 microM, n = 5, p < 0.05) from hCBMCs compared to control cells (182 +/- 57 pg/106 cells), and IL-6 release (466 +/- 57 pg/106 cells at 0.1 microM) compared to untreated cells (13 +/- 25 pg/106 cells, n = 5, p < 0.05). Addition of HgCl2 (0.1 microM) to SP (5 microM) further increased IL-6 release.
  
  
  CONCLUSIONS
  HgCl2 stimulates VEGF and IL-6 release from human mast cells. This phenomenon could disrupt the blood-brain-barrier and permit brain inflammation. As a result, the findings of the present study provide a biological mechanism for how low levels of mercury may contribute to ASD pathogenesis.
authors.affiliation: Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts Medical Center, Boston, MA 02111, USA.
authors.forename: Duraisamy
authors.initials: D
authors.lastname: Kempuraj
authors.forename: Shahrzad
authors.initials: S
authors.lastname: Asadi
authors.forename: Bodi
authors.initials: B
authors.lastname: Zhang
authors.forename: Akrivi
authors.initials: A
authors.lastname: Manola
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hogan
authors.forename: Erika
authors.initials: E
authors.lastname: Peterson
authors.forename: Theoharis C
authors.initials: TC
authors.lastname: Theoharides
mesh_terms: D001321:Autistic Disorder / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006632:Histamine / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D008627:Mercuric Chloride / Q000378:metabolism / Q000633:toxicity*; D013373:Substance P / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D042461:Vascular Endothelial Growth Factor A; D013373:Substance P; D008627:Mercuric Chloride; D006632:Histamine; D001619:beta-N-Acetylhexosaminidases