Figure 2.

Overview of the main lipoxin biosynthetic pathways. In the PMN cell, Arachidonic Acid (AA) can be converted into either 15S-HpETE or Leukotriene A₄ (LTA4) by 15-LO and 5-LO, respectively. Then, these metabolites are transformed into native lipoxin A₄ or B₄. Moreover, platelets can use LTA₄ from PMNs to produce LXA₄/B₄ in a process known as transcellular biosynthesis. Likewise, in epithelial cells AA is transformed by 15-LO into 15-HETE, which is transferred to PMNs to produce LXA₄/B₄. Endothelial cells can use AA to yield the intermediate 15R-HETE by COX-2, step that is promoted by aspirin. This transitional molecule is metabolized by PMNs to generate the “aspirin-triggered” 15-epi-lipoxins A₄ and B₄. Finally, both native and aspirin-triggered LXs can be rapidly inactivated by 15-PGDH, stopping the downstream signaling.