title: Inorganic arsenite inhibits IgE receptor-mediated degranulation of mast cells.
abstract: Millions of people worldwide are exposed to arsenic (As), a toxicant which increases the risk of various cancers, cardiovascular disease and several other health problems. Arsenic is a potent endocrine disruptor, including of the estrogen receptor. It was recently shown that environmental estrogen-receptor disruptors can affect the signaling of mast cells, which are important players in parasite defense, asthma and allergy. Antigen (Ag) or allergen crosslinking of IgE-bound receptors on mast cells leads to signaling, culminating in degranulation, the release of histamine and other mediators. Because As is an endocrine disruptor and because endocrine disruptors have been found to affect degranulation, here we have tested whether sodium arsenite affects degranulation. Using the rat basophilic leukemia (RBL) mast cell model, we have measured degranulation in a fluorescence assay. Arsenic alone had no effect on basal levels of degranulation. However, As strongly inhibited Ag-stimulated degranulation at environmentally relevant concentrations, in a manner that is very dependent on concentrations of both As and Ag. The concentrations of As effective at inhibiting degranulation were not cytotoxic. This inhibition may be a mechanism underlying the traditional Chinese medicinal use of As to treat asthma. These data indicate that As may inhibit the ability of humans to fight off parasitic disease.
authors.affiliation: Department of Molecular & Biomedical Sciences, University of Maine, Orono, ME 04469, USA.
authors.forename: Lee M
authors.initials: LM
authors.lastname: Hutchinson
authors.forename: Benett M
authors.initials: BM
authors.lastname: Trinh
authors.forename: Rachel K
authors.initials: RK
authors.lastname: Palmer
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Preziosi
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Pelletier
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Nelson
authors.forename: Julie A
authors.initials: JA
authors.lastname: Gosse
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018053:Arsenites / Q000633:toxicity*; D015550:Cell Degranulation / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004359:Drug Therapy, Combination; D052244:Endocrine Disruptors / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017455:Receptors, IgE / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D017670:Sodium Compounds / Q000633:toxicity*; D014343:Trypan Blue / Q000378:metabolism
chemical_list: D000485:Allergens; D000911:Antibodies, Monoclonal; D018053:Arsenites; D052244:Endocrine Disruptors; D017455:Receptors, IgE; D017670:Sodium Compounds; C017947:sodium arsenite; D007770:L-Lactate Dehydrogenase; D014343:Trypan Blue