Lipid-derived lipoxins are produced at the site of vascular and mucosal inflammation where they down-regulate polymorphonuclear leukocyte recruitment and function. 5(S),6(R),15(R)-Lipoxin A₄ (5(S),6(R),15(R)-LXA₄) is derived from the aspirin-triggered formation of 15(R)-HETE from arachidonic acid.^1,2 5(S),6(R),15(R)-LXA₄ inhibits LTB₄-induced chemotaxis, adherence, and transmigration of neutrophils with twice the potency of LXA₄ demonstrating activity in the nM range.^3,2 The anti-inflammatory effects of aspirin may be ascribed in part to the ability of 5(S),6(R),15(R)-LXA₄ to regulate leukocyte function.⁴

1 Clària, J., Lee, M.H., Serhan, C.N. Aspirin-triggered lipoxins (15-epi-LX) are generated by the human lung adenocarcinoma cell line (A549)-neutrophil interactions and are potent inhibitors of cell proliferation. Mol Med 2 583-596 (1996).

2 Clària, J., Serhan, C.N. Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell-leukocyte interactions. Proc Natl Acad Sci USA 92 9475-9479 (1995).

3 Fierro, I.M., Colgan, S.P., Bernasconi, G., et al. Lipoxin A₄ and aspirin-triggered 15-epi-lipoxin A₄ inhibit human neutrophil migration: Comparisons between synthetic 15 epimers in chemotaxis and transmigration with microvessel endothelial cells and epithelial cells. J Immunol 170 2688-2694 (2003).

4 Chiang, N., Bermudez, E.A., Ridker, P.M., et al. Aspirin triggers antiinflammatory 15-epi-lipoxin A₄ and inhibits thromboxane in a randomized human trial. Proc Natl Acad Sci USA 101(42) 15178-15183 (2004).

Chiang, N., Bermudez, E.A., Ridker, P.M., et al. Aspirin triggers antiinflammatory 15-epi-lipoxin A₄ and inhibits thromboxane in a randomized human trial. Proc Natl Acad Sci USA 101(42) 15178-15183 (2004).

Fierro, I.M., Colgan, S.P., Bernasconi, G., et al. Lipoxin A₄ and aspirin-triggered 15-epi-lipoxin A₄ inhibit human neutrophil migration: Comparisons between synthetic 15 epimers in chemotaxis and transmigration with microvessel endothelial cells and epithelial cells. J Immunol 170 2688-2694 (2003).

Clària, J., Serhan, C.N. Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell-leukocyte interactions. Proc Natl Acad Sci USA 92 9475-9479 (1995).

Clària, J., Lee, M.H., Serhan, C.N. Aspirin-triggered lipoxins (15-epi-LX) are generated by the human lung adenocarcinoma cell line (A549)-neutrophil interactions and are potent inhibitors of cell proliferation. Mol Med 2 583-596 (1996).

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