Lipoxins and Aspirin-Triggered Lipoxins in Airway Responses

Leukotrienes (LT) and prostaglandins (PG) have been implicated as proinflammatory mediators in asthma [1], while lipoxins (LX) are a distinct class of eicosanoids that carry unique counter-regulatory actions [2]. Analyses of the time course of appearance of eicosanoids during acute inflammation has revealed the early coordinate appearance of LT and PG with leukocyte recruitment followed by LX during resolution [3]. LX’s are generated in human tissues, including airways [4], and can interact with at least two classes of receptors, CysLT1 and LXA4 receptors (designated ALX) [5]. LX’s, aspirin-triggered 15-epimer-LX’s and stable, longer-acting analogs of these compounds can promote resolution of cytokine-driven acute inflammation [5], inhibit LTC4-stimulated airway hyper-responsiveness in human asthmatics [6] and block LTD4-initiated constriction of airway smooth muscle in vitro [7]. of note, aspirin-tolerant asthmatic individuals have a decreased biosynthetic capacity for LX’s [8]. In view of these intriguing findings, we determined the impact of LX’s in an experimental murine model of asthma [9].