N-formyl peptide receptor 2/LX A4 receptor (FPR2/ALX)
Originally FPR2 was classified as an FPR receptor due to its activation by the low-affinity endogenous agonist N-formyl methionyl peptide (fMLP) (Ye et al. 1992). The receptor was reclassified as FPR2/ALX, as LXA4 exhibited the highest affinity of all FPR2/ALX endogenous agonists through screening of various receptor ligands using radiolabelled [3H]-LXA4 and subsequent GTPase activity (Fiore et al. 1994; Brink et al. 2003). Binding of LXA4 leads to the stimulation of monocyte chemotaxis, macrophage differentiation, and efferocytosis (Maderna et al. 2010; Maddox and Serhan 1996). LXA4 also reduces the adaptive immune response by reducing memory B cell antibody production and proliferation (Ramon et al. 2014).
Endogenous and exogenous lipids, peptides, and proteins have been shown to bind and activate FPR2/ALX to produce inflammatory and anti-inflammatory effects (Takano et al. 1997; Cooray et al. 2013). Both the LXs and Rvs families, including LXA4, AT-LXA4 (15-epi-LXA4), RvD1, AT-RvD1 (17-epi-RvD1), and Annexin A1 (ANXA1) activate receptors with high potency. On the other hand, endogenous antagonists, including serum amyloid A (SAA) and cathelicidin (LL-37) have been identified (Bozinovski et al. 2012; Wan et al. 2011).