Abstract
The cysteinyl leukotrienes (cys-LTs) are powerful inflammatory mediators that can be produced by both murine and human dendritic cells (DCs) in response to extracts from house dust mite, but the molecular mechanism is unknown. We have evaluated the requirements for cys-LT generation by murine bone marrow-derived DCs (BMDCs) in response to allergen extracts from the fungus Aspergillus fumigatus (Af), and the house mites Dermatophagoides pteronyssinus (Dp), and Dermatophagoides farinae (Df). BMDCs were generated with granulocyte macrophage colony stimulating factor and evaluated between day 8 and 10. BMDCs produced cys-LTs to extracts from Af, Dp, and Df that peaked by 30 min. There was no response to ovalbumin with or without lipopolysaccharide, to TLR2 agonists, or to NOD agonists. Treatment of the Df extract with heat, nucleases, or proteases did not diminish its activity, and after chloroform-methanol extraction the activity was retained in the aqueous phase. Recombinant Df did not elicit cys-LT production. These results demonstrate that DCs recognize a highly polar, non-proteinous agonist(s) in several common allergens that elicits a rapid and robust production of cys-LTs.
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