title: Polycyclic aromatic hydrocarbons from diesel emissions exert proallergic effects in birch pollen allergic individuals through enhanced mediator release from basophils.
abstract: BACKGROUND
  Diesel exhaust particles (DEPs) act as adjuvants in the immune system and contribute to the increased prevalence and morbidity of asthma and allergic rhinitis. Polycyclic aromatic hydrocarbons (PAHs) are major components of DEPs, which may be involved in the induction and enhancement of proallergic processes. In this study we explored adjuvant effects of DEP-PAHs on activation parameters of human basophils, fostering allergic inflammation through the release of preformed or granule-derived mediators.
  
  
  METHODS
  Heparinized blood samples from birch pollen allergic and control donors were stimulated with Bet v 1, the major allergen of birch pollen grains, alone or together with a mixture of 16 environmental prominent PAHs (EPA-PAH standard). Flow cytometric analysis was performed for quantitative determination of PAH-enhanced basophil activation. To assess direct PAH effects on basophils, enriched cultures from both donor groups were exposed to benzo[a]pyrene (B[a]P) or phenanthrene (Phe), two major DEP-PAHs, with and without allergen. Supernatants were assayed for IL-4 and IL-8 secretion and histamine release by means of ELISA.
  
  
  RESULTS
  At environmental relevant exposure levels EPA-PAH standard synergized with antigen and significantly enhanced basophil activation of all birch pollen allergic individuals up to 95%. Single PAHs significantly drove IL-8 secretion from sensitized basophils of all patients tested, and there was no further enhancement by addition of rBet v 1. B[a]P and Phe also significantly induced IL-4 secretion, a key factor for Th2 development, from purified sensitized basophils in the absence of antigen suggesting an adjuvant role of DEP-PAHs in allergic sensitization. None of the basophil samples from healthy controls showed any PAH effect on mediator release.
  
  
  CONCLUSIONS
  DEP-PAHs exert proallergic effects on sensitized basophils in an allergen independent fashion, suggesting a potential role of these pollutants for the allergic breakthrough in atopic individuals, who have not developed an allergic disease yet.
authors.affiliation: Division of Environmental Dermatology and Allergy, Helmholtz Zentrum München/TUM, ZAUM - Center for Allergy and Environment, Technische Universität München, 80802 Munich, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Lubitz
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schober
authors.forename: Gudrun
authors.initials: G
authors.lastname: Pusch
authors.forename: Renate
authors.initials: R
authors.lastname: Effner
authors.forename: Norman
authors.initials: N
authors.lastname: Klopp
authors.forename: Heidrun
authors.initials: H
authors.lastname: Behrendt
authors.forename: Jeroen T M
authors.initials: JT
authors.lastname: Buters
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D000393:Air Pollutants / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism; D052179:Antigens, Plant / Q000276:immunology*; D001491:Basophils / Q000187:drug effects / Q000276:immunology*; D001564:Benzo(a)pyrene / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006632:Histamine / Q000378:metabolism; D006801:Humans; D008297:Male; D052638:Particulate Matter / Q000494:pharmacology; D010616:Phenanthrenes / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011084:Polycyclic Aromatic Hydrocarbons / Q000494:pharmacology*; D006255:Rhinitis, Allergic, Seasonal / Q000235:genetics / Q000276:immunology*; D060149:Tetraspanin 30; D001335:Vehicle Emissions; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000393:Air Pollutants; D015703:Antigens, CD; D052179:Antigens, Plant; C554586:CD63 protein, human; D016207:Cytokines; D052638:Particulate Matter; D010616:Phenanthrenes; D010980:Platelet Membrane Glycoproteins; D011084:Polycyclic Aromatic Hydrocarbons; D060149:Tetraspanin 30; D001335:Vehicle Emissions; D001564:Benzo(a)pyrene; C031181:phenanthrene; D006632:Histamine