15epiLXA4

15epiLXA4, short for 15-epi-lipoxin A4, also known as aspirin-triggered lipoxin A4 (ATL), is a specialized pro-resolving lipid mediator formed from arachidonic acid. It is an epimer of the classical lipoxin A4 at carbon 15, produced when aspirin acetylates cyclooxygenase-2 (COX-2), redirecting arachidonic acid metabolism to generate 15R-hydroxy-eicosatetraenoic acid (15R-HETE), which is then converted by 5-lipoxygenase to 15-epi-LXA4.

As a mediator of resolution, 15epiLXA4 has anti-inflammatory and pro-resolving actions, including inhibition of neutrophil influx and adhesion, reduction of vascular permeability, and stimulation of macrophage clearance of apoptotic cells. It primarily signals through the ALX/FPR2 G protein-coupled receptor, though interactions with other receptors may contribute to its effects.

15epiLXA4 is detected in inflamed tissues and biological fluids, particularly in situations of aspirin use or aspirin-induced COX-2 acetylation. In preclinical studies, aspirin-triggered lipoxins contribute to the anti-inflammatory benefits of aspirin in models of airway disease, arthritis, and tissue injury, and are considered part of the broader family of specialized pro-resolving mediators.

Chemically, it is the 15-epi isomer of LXA4, distinguished by the configuration at carbon 15; thus it shares the same backbone and three hydroxyl groups but differs at C-15 from native LXA4. It is typically measured by targeted lipidomics using mass spectrometry.