Lipoxin A4 inhibits acute edema in mice:: Implications for the anti-edematogenic mechanism induced by aspirin

Lipoxin A(4) (LXA(4)) is a lipid mediator that plays an important role in the resolution of inflammation. However, the role of LXA(4) and aspirin (ASA)-triggered lipoxins (ATLs) in inflammatory edema formation remains unclear. Here, we investigated the inhibitory role played by LXA(4) in the carrageenan-induced and other inflammatory mediator-induced edematogenic response in mice, and also assessed the role of ATLs in the anti-edematogenic action of aspirin. Our results showed that LXA(4) (1-20 ng/paw or 5 mu g/kg i.p.) was effective in inhibiting carrageenan-induced paw edema from 30 min to 2 h. LXA(4) (10 ng/paw) was also able to acutely inhibit PAF-, histamine-, PGE(2)- or bradykinin-induced paw edema, as well as the PAF-induced myeloperoxidase activity increase in the paws. Likewise, LXA(4) (10 ng/cavity) also inhibited the pleural edema triggered by histamine (1 h), and this response was not followed by leukocyte accumulation. Of note, the lipoxin receptor (ALX-r) antagonist Boc2 (butoxycarbonyl-Phe-Leu-Phe-Leu-Phe, 200 ng/paw) significantly reverted the anti-edematogenic effect of ASA (300 mg/kg p.o.) against carrageenan, PAF, PGE(2) and BK, without affecting the anti-edematogenic action caused by indomethacin (3 mg/kg i.p.) in the carrageenan-induced paw edema. Collectively, our results demonstrate for the first time that LXA4 displays an acute and rapid onset anti-edematogenic activity that does not discriminate among different pro-inflammatory stimuli, an effect that is most likely independent of its action on the leukocyte influx. Finally, the present study demonstrates that ATLs exert a very important role in the acute anti-edematogenic action of ASA. (c) 2006 Elsevier Inc. All rights reserved.