The role of Formyl peptide receptor 2 (Fpr2) in leukocytes trafficking

Vincenzo Brancaleone, Neil Dufton, Jesmond Dalli, Roderick J Flower, Mauro Perretti. WHRI - Queen Mary University of London, London, United Kingdom.

Active resolution of inflammation is a relatively novel concept that represents the response of innate immunity to inflammatory stimuli. This response involves various mediators, including annexin-A1 and lipoxin A4, that exert their actions by activating specific G-protein coupled receptor of the formyl-peptide receptor family (FPR; human FPRs have been re-named as FPR1, FPR2 and FPR3), with particular efficacy on FPR2.

In this study we used Fpr2-/- mice to study the inflammatory phenotype, using in vivo techniques such as intravital microscopy (IVM) of inflamed mesenteries (challenged with an ischemia-reperfusion protocol) and carrageenan-induced paw oedema.

IVM study showed that cell adhesion and emigration were both significantly increased (∼3 fold) in Fpr2-/- mice in non-inflammatory conditions. Furthermore, the increase in cell emigration induced by ischemia-reperfusion model (30-45 min) was greater in Fpr2-/- than in Fpr2+/+ mice used as controls (8.0 vs 4.5 cells per 50x100μm2, Fpr2-/- vs Fpr2+/+). Instead, there was no significant change in leukocytes rolling velocity. The difference observed after 45 min reperfusion was even more evident when a 90 min reperfusion period was used, doubling the number of both emigrated and adherent cells (P<0.01).

Paw oedema results showed a more inflamed profile for Fpr2-/- mice than Fpr2+/+, in both its first and second phase (peaking at 6h and 72 h, respectively).

These results show that Fpr2-/- mice have an unbalanced inflammatory response, confirming the prominent role for Fpr2 receptor in resolution of inflammation. Fpr2 agonists would be viable novel anti-inflammatory therapeutics.

Funded by the Wellcome Trust (programme grant 086867/Z/08/Z).