The lipoxin receptor ALX: potent ligand-specific and stereoselective actions in vivo

N Chiang, CN Serhan, SE Dahlén, JM Drazen… - Pharmacological …, 2006 - ASPET
Pharmacological reviews, 2006ASPET
Lipoxins (LXs) and aspirin-triggered LX (ATL) are trihydroxytetraene-containing eicosanoids
generated from arachidonic acid that are distinct in structure, formation, and function from
the many other proinflammatory lipid-derived mediators. These endogenous eicosanoids
have now emerged as founding members of the first class of lipid/chemical mediators
involved in the resolution of the inflammatory response. Lipoxin A4 (LXA4), ATL, and their
metabolic stable analogs elicit cellular responses and regulate leukocyte trafficking in vivo …
Lipoxins (LXs) and aspirin-triggered LX (ATL) are trihydroxytetraene-containing eicosanoids generated from arachidonic acid that are distinct in structure, formation, and function from the many other proinflammatory lipid-derived mediators. These endogenous eicosanoids have now emerged as founding members of the first class of lipid/chemical mediators involved in the resolution of the inflammatory response. Lipoxin A4 (LXA4), ATL, and their metabolic stable analogs elicit cellular responses and regulate leukocyte trafficking in vivo by activating the specific receptor, ALX. ALX was the first receptor cloned and identified as a G protein-coupled receptor (GPCR) for lipoxygenase-derived eicosanoids with demonstrated cell type-specific signaling pathways. ALX at the level of DNA has sequence homology to the N-formylpeptide receptor and as an orphan GPCR was initially referred to as the N-formylpeptide receptor-like 1. Although LXA4 is the endogenous potent ligand for ALX activation, a number of peptides can also activate this receptor to stimulate calcium mobilization and chemotaxis in vitro. In contrast with LXA4, the counterparts of many of these peptides in vivo remain to be established. The purpose of this review is to highlight the molecular characterization of the ALX receptor and provide an overview of the ALX-LXA4 axis responsible for anti-inflammatory and proresolving signals in vivo. The information in this review provides further support for the initial nomenclature proposition for this GPCR as ALX.
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