Cutting edge:: Lipoxin (LX) A4 and aspirin-triggered 15-Epi-LXA4 block allergen-induced eosinophil trafficking

Tissue eosinophilia prevention represents one of the primary targets to new anti-allergic therapies. As lipoxin A(4) (LXA(4)) and aspirin-triggered 15-epi-LXA(4) (ATL) are emerging as endogenous "stop signals" produced in distinct pathologies including some eosinophil-related pulmonary disorders, we evaluated the impact of in situ LXA(4)/ATL metabolically stable analogues on allergen-induced eosinophilic pleurisy in sensitized rats. LXA(4)/ATL analogues dramatically blocked allergic pleural eosinophil influx, while concurrently increasing circulating eosinophilia, inhibiting the earlier edema and neutrophilia associated with allergic reaction. The mechanisms underlying this LXA(4)/ATL-driven allergic eosinophilia blockade was independent of mast cell degranulation and involved LXA(4)/ATL inhibition of both IL-5 and eotaxin generation, as well as platelet activating factor action. These findings reveal LXA(4)/ATL as a novel class of endogenous anti-allergic mediators, capable of preventing local eosinophilia.