Polycyclic aromatic hydrocarbons from diesel emissions exert proallergic effects in birch pollen allergic individuals through enhanced mediator release from basophils.

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. CONCLUSION: 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.

Environmental polycyclic aromatic hydrocarbons (PAHs) enhance allergic inflammation by acting on human basophils.

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.

Organic extracts of urban aerosol (< or =PM2.5) enhance rBet v 1-induced upregulation of CD63 in basophils from birch pollen-allergic individuals.

Epidemiological studies have linked the high prevalence rates of IgE-mediated allergic diseases to an increase in exposure to traffic-related air pollutants such as diesel exhaust particles (DEPs). There is growing experimental evidence that organic compounds of DEPs, predominantly polycyclic aromatic hydrocarbons (PAHs), participate in the development and maintenance of allergic airway diseases. In this study we investigated the impact of organic extracts of urban aerosol (AERex) containing various PAH concentrations on the activation of human basophils. Whole blood samples from six birch pollen-allergic and five control subjects were repeatedly incubated in the presence of AERex with or without recombinant Bet v 1 (rBet v 1). Basophils were analyzed for CD63 expression as a measure of basophil activation by using multiparameter flow cytometry. Basophils, when exposed in vitro to AERex and rBet v 1, expressed CD63 significantly more than with antigen activation alone. AERex synergized with rBet v 1 in a dose-dependent manner, but did not activate basophils from nonallergic donors. AERex effect on CD63 upregulation was found in blood samples of all patients and did not occur in the absence of rBet v 1. Strongest basophil activation was monitored upon stimulation with AERex comprising the highest PAH content. The capability of AERex to increase activation of basophils from birch pollen-allergic subjects at ambient concentrations suggests an important role of organic compounds of airborne particles in the aggravation of IgE-mediated allergic diseases. This could be a new aspect of regulation of unspecific promoting stimuli in clinical manifestation of allergic inflammation.