title: Environmental polycyclic aromatic hydrocarbons (PAHs) enhance allergic inflammation by acting on human basophils.
abstract: Diesel exhaust particles (DEPs) have been implicated in the worldwide increased incidence of allergic airway diseases over the past century. There is growing evidence that DEP-associated polycyclic aromatic hydrocarbons (PAHs) participate in the development and maintenance of immunoglobulin (Ig) E-mediated allergic diseases. To address this issue we investigated the impact of U.S. Environmental Protection Agency (EPA) priority PAHs as well as of PAH-containing airborne extracts on antigen-induced CD63 upregulation and mediator release from human basophils. Whole blood samples from birch pollen allergic and control subjects were incubated in the presence of organic extracts of urban aerosol (AERex) or EPA-PAH standard with or without rBet v 1. Basophils were analyzed for CD63 expression as a measure of basophil activation by using multiparameter flow cytometry. In addition, purified basophils from birch pollen allergic donors were incubated for 2 h in the presence of 1 muM benzo[a]pyrene (BaP) or phenanthrene (Phe) and then stimulated with rBet v 1 for 45 min. Supernatants were assayed for histamine, interleukin (IL)-4, and IL-8 by means of enzyme-linked immunosorbent assay (ELISA). Basophils exposed in vitro simultaneously to AERex or EPA-PAH standard and rBet v 1 expressed CD63 significantly more than with antigen alone. PAHs synergized with rBet v 1 dose dependently, but did not activate basophils from nonallergic donors. BaP and Phe significantly enhanced cytokine secretion (IL-4, IL-8) and histamine release from purified basophils without antigen added, and secretion was not further enhanced by rBet v 1 stimulation. In conclusion, PAHs from roadside emissions can directly activate sensitized basophils to cytokine secretion and drive proallergic processes through enhanced Fcepsilon RI-coupled mediator release from human basophils.
authors: Division of Environmental Dermatology and Allergy GSF/TUM, ZAUM-Center for Allergy and Environment, Technical University Munich, Munich, Germany. schober@lrz.tum.de
authors: Wolfgang
authors: W
authors: Schober
authors: Stefanie
authors: S
authors: Lubitz
authors: Benedetta
authors: B
authors: Belloni
authors: Gudrun
authors: G
authors: Gebauer
authors: Jutta
authors: J
authors: Lintelmann
authors: Georg
authors: G
authors: Matuschek
authors: Ingrid
authors: I
authors: Weichenmeier
authors: Bernadette
authors: B
authors: Eberlein-König
authors: Jeroen
authors: J
authors: Buters
authors: Heidrun
authors: H
authors: Behrendt
mesh_terms: D001491:Basophils / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D004781:Environmental Exposure / Q000009:adverse effects*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology; D052638:Particulate Matter / Q000633:toxicity; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*
chemical_list: D052638:Particulate Matter; D011084:Polycyclic Aromatic Hydrocarbons