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 A4 (LXA4) and aspirin-triggered 15-epi-LXA4 (ATL) are emerging as endogenous "stop signals" produced in distinct pathologies including some eosinophil-related pulmonary disorders, we evaluated the impact of in situ LXA4/ATL metabolically stable analogues on allergen-induced eosinophilic pleurisy in sensitized rats. LXA4/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 LXA4/ATL-driven allergic eosinophilia blockade was independent of mast cell degranulation and involved LXA4/ATL inhibition of both IL-5 and eotaxin generation, as well as platelet activating factor action. These findings reveal LXA4/ATL as a novel class of endogenous anti-allergic mediators, capable of preventing local eosinophilia.
Bandeira-Melo
C
C
Department of Physiology and Pharmacodynamics, Oswaldo Cruz Institute, Fundaçao Oswaldo Cruz, Rio de Janeiro, Brazil.
Bozza
P T
PT
Diaz
B L
BL
Cordeiro
R S
RS
Jose
P J
PJ
Martins
M A
MA
Serhan
C N
CN
D000485:Allergens / Q000276:immunology*; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D001241:Aspirin / Q000008:administration & dosage*; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004802:Eosinophilia / Q000276:immunology / Q000473:pathology; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology*; D005260:Female; D006893:Hydroxyeicosatetraenoic Acids / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D044045:Lipoxins; D008297:Male; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010998:Pleurisy / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar
D000485:Allergens; D018926:Anti-Allergic Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D006893:Hydroxyeicosatetraenoic Acids; D044045:Lipoxins; C040527:lipoxin A4; D010047:Ovalbumin; D001241:Aspirin