Lipoxin

Lipoxins are a series of anti-inflamatory mediators. Lipoxins are short lived endogenously produced eicosanoids whose appearance in inflammation signals the resolution of inflammation. During the acute inflammatory process, the proinflammatory cytokines such as IFN-&gamma; and IL-1&beta; can induce the expression of anti-inflammatory mediators such as lipoxins (LXs) and IL-4, which promote the resolution phase of inflammation. They are abbreviated as LX, an acronym for lipoxygenase (LO) interaction products. Lipoxins are derived from arachidonic acid, an &omega;-6 fatty acid An analogous class, the resolvins, is derived from EPA and DHA, &omega;-3 fatty acids. At present two lipoxins have been identified; lipoxin A4 (LXA4) and lipoxin B4 (LXB4).

Lipoxins, as well as certain peptides, are high affinity (sub nanomolar) ligands for the lipoxin A4 receptor (ALXR), which was first identified based on sequence homology as the formyl peptide receptor like receptor (FPRL1). Lipoxin signaling through the ALXR inhibits chemotaxis, transmigration, superoxide generation and NF-kB activation.

Conversely, peptide signalling through the same receptor, in vitro, has been shown to stimulate chemotaxis of PMN and calcium mobilization. The peptides that have ALXR affinity tend to be signals for leukocyte migration and subsequent phagocytosis such as acute phase proteins, bacterial peptides, HIV envelope proteins and neurotoxic peptides.

Lipoxins are also high affinity antagonists to the cystienyl leukotriene receptor 1 (CysLT1) to which several leukotrienes (LTC4, LTD4 and LTE4) mediate their smooth muscle contraction and eosinophil chemotactic effects. The CysLT1 receptor is also the site of action for the asthma drug, Montelukast(Singulair)