Abstract
Polycyclic aromatic hydrocarbons (PAHs) are major components of diesel exhaust particles found in pollutant respirable particles. There is growing evidence that these fossil fuel combustion products exacerbate allergic inflammation. Basophils contribute to allergic inflammation through the release of preformed and granule-derived mediators. To determine whether allergens and PAHs interact, we incubated human basophils with PAHs and measured the release of histamine and IL-4 with and without added antigen. None of the PAHs induced mediator release by itself and none affected total cellular histamine levels. However, several PAHs enhanced histamine release and IL-4 production in response to crosslinking the high-affinity IgE receptor, FcεRI. The enhancement seen with 1,6-BaP-quinone involved an increase in tyrosine phosphorylation in several different substrates, including the FcεRI-associated tyrosine kinase, Lyn, and elevated reactive oxygen species (ROS) levels detected by dichlorofluorescein fluorescence and flow cytometry. The PAH-induced enhancement of mediator release and ROS production could be inhibited with the antioxidant N-acetylcysteine. These data provide further evidence that environmental pollutants can influence allergic inflammation through enhanced FcεRI-coupled mediator release from human basophils.
Highlights
Polycyclic aromatic hydrocarbons (PAHs) are major components of diesel exhaust particles found in pollutant respirable particles
No IL-4 production was observed when basophils were challenged with PAHs alone
The PAHs 1,6-BPQ and 3,6-BPQ, but not BaP, significantly enhanced IgE-mediated IL-4 production (Fig. 2).These data suggest that some metabolites of BaP and perhaps associated with Diesel exhaust particles (DEPs) and other particulate matter (PM) found in air pollution may enhance human allergic inflammation via enhanced mediator release from basophils
Summary
Polycyclic aromatic hydrocarbons (PAHs) are major components of diesel exhaust particles found in pollutant respirable particles. The PAH-induced enhancement of mediator release and ROS production could be inhibited with the antioxidant N-acetylcysteine These data provide further evidence that environmental pollutants can influence allergic inflammation through enhanced FcεRI-coupled mediator release from human basophils. To determine whether BaP or any of its known major metabolites may be involved in activation of signaling pathways associated with mediator release from human basophils, we exposed human basophils to BaP and several of its P450 and non-P450 breakdown products. We found that BaP and several BaP-quinones (BPQs) could enhance IgE-mediated histamine release and cytokine production by altering specific signaling pathways. Our data suggest that BPQs or other related oxidative agents present in or on DEP can trigger allergic inflammation through enhanced antigen-induced mediator release from human basophils through oxidative-stress-associated pathways
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