Lipoxin Receptors

Lipoxins (LXs) represent a class of arachidonic acid (AA) metabolites that carry potent immunoregulatory and anti-inflammatory properties, LXA(4) and LXB(4) being the main components of this series. LXs are generated by cooperation between 5-lipoxygenase (LO) and 12- or 15-LO during cell-cell interactions or by single cell types. LX epimers at carbon 15, the 15-epi-LXs, are formed by aspirin-acetylated cyclooxygenase-2 (COX-2) in cooperation with 5-LO. 15-epi-LXA(4) is also termed aspirin-triggered LX (ATL). In vivo studies with stable LX and ATL analogs have established that these eicosanoids possess potent anti-inflammatory activities. A LXA(4) receptor has been cloned. It belongs to the family of chemotactic receptors and clusters with formyl peptide receptors on chromosome 19. Therefore, it was initially denominated formyl peptide receptor like 1 (FPRL1). This receptor binds with high affinity and stereoselectivity LXA(4) and ATL. It also recognizes a variety of peptides, synthetic, endogenously generated, or disease associated, but with lower affinity compared to LXA(4). For this reason, this receptor has been renamed ALX. This review summarizes the current knowledge on ALX expression, signaling, and potential pathophysiological role. The involvement of additional recognition sites in LX bioactions is also discussed.