title: Chronic arsenic exposure in nanomolar concentrations compromises wound response and intercellular signaling in airway epithelial cells.
abstract: Paracrine ATP signaling in the lung epithelium participates in a variety of innate immune functions, including mucociliary clearance, bactericide production, and as an initiating signal in wound repair. We evaluated the effects of chronic low-dose arsenic relevant to U.S. drinking water standards (i.e., 10 ppb [130nM]) on airway epithelial cells. Immortalized human bronchial epithelial cells (16HBE14o-) were exposed to 0, 130, or 330nM arsenic (as Na-arsenite) for 4-5 weeks and examined for wound repair efficiency and ATP-mediated Ca(2+) signaling. We found that chronic arsenic exposure at these low doses slows wound repair and reduces ATP-mediated Ca(2+) signaling. We further show that arsenic compromises ATP-mediated Ca(2+) signaling by altering both Ca(2+) release from intracellular stores (via metabotropic P2Y receptors) and Ca(2+) influx mechanisms (via ionotropic P2X receptors). To better model the effects of arsenic on ATP-mediated Ca(2+) signaling under conditions of natural exposure, we cultured tracheal epithelial cells obtained from mice exposed to control or 50 ppb Na-arsenite supplemented drinking water for 4 weeks. Tracheal epithelial cells from arsenic-exposed mice displayed reduced ATP-mediated Ca(2+) signaling dynamics similar to our in vitro chronic exposure. Our findings demonstrate that chronic arsenic exposure at levels that are commonly found in drinking water (i.e., 10-50 ppb) alters cellular mechanisms critical to airway innate immunity.
authors.affiliation: Arizona Respiratory Center, University of Arizona, Tucson, AZ, USA.
authors.forename: Cara L
authors.initials: CL
authors.lastname: Sherwood
authors.forename: R Clark
authors.initials: RC
authors.lastname: Lantz
authors.forename: Scott
authors.initials: S
authors.lastname: Boitano
mesh_terms: D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D060888:Real-Time Polymerase Chain Reaction; D058469:Receptors, Purinergic P2X / Q000378:metabolism; D058470:Receptors, Purinergic P2Y / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D058469:Receptors, Purinergic P2X; D058470:Receptors, Purinergic P2Y; D001151:Arsenic