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TheScientificWorldJOURNAL
Volume 10, Pages 1048-1064
http://dx.doi.org/10.1100/tsw.2010.113
Review Article

Lipoxin and Aspirin-Triggered Lipoxins

Department of Biomedical Sciences, Aging Research Center, Ce.S.I., “Gabriele D'Annunzio” University Foundation, Chieti, Italy

Received 7 March 2010; Revised 7 March 2010; Accepted 13 May 2010

Academic Editor: Joan Cl�a

Copyright © 2010 Mario Romano.

Abstract

Lipoxins and their 15 epimers, aspirin triggered lipoxins (ATL), are eicosanoids derived from sequential lipoxygenase (LO) metabolism of arachidonic acid. The main routes of lipoxin biosynthesis involve cooperation between 15- and 5-LO, and between 12- and 5-LO. ATL are generated by interactions between 5-LO and aspirin-acetylated cyclooxygenase-2. Cellular models recapitulating these interactions involve leukocytes, platelets, vascular endothelium, and epithelium. To circumvent rapid lipoxin and ATL metabolism and inactivation, stable analogs, bearing potent and long-lasting biological activity, have been synthesized. Some of these analogs displayed therapeutic potential by showing strong anti-inflammatory activity in a number of animal models of disease, including reperfusion injury; arthritis; gastrointestinal, renal, respiratory, and vascular inflammatory disorders; eye damage; periodontitis; and selected infectious diseases. Counter-regulatory signaling by lipoxin A4 and 15-epi-lipoxin A4 is triggered by the activation of a seven-transmembrane domain receptor, termed FPR2/ALX, which is highly expressed in myeloid cells and has been recognized as a main anti-inflammatory receptor.