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FPR2/ALX as an Anti‐inflammatory Target in the Treatment of Sepsis
Author(s) -
Hughes Ellen L,
Buckingham Julia C,
Gavins Felicity Nicola
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.638.20
Sepsis is a syndrome with few treatment options, causing around 1.8m deaths worldwide each year. It is frequently associated with bacterial infection and is characterised by a hyperactive systemic inflammatory response. A potential target for anti‐inflammatory therapeutics is formyl peptide receptor 2 (FPR2/ALX), which is highly expressed in leukocytes. This study was conducted to investigate the anti‐inflammatory properties of FPR2/ALX in sepsis. Experimental endotoxaemia was induced in C56BL/6 mice (i.p. lipopolysaccharide (LPS; 10 μg/mouse; n=5 mice/group)). After 20 min a drug was injected into the tail vein, and after 2h the inflammatory response was assessed in terms of leukocyte‐endothelium interactions, by intravital microscopy of the mesenteric vascular bed. The FPR2/ALX agonists, Ac2‐26 and LXA4, reduced LPS‐induced leukocyte adherence by approximately 60% and 55%, respectively. Both agonists' anti‐adhesive effects were blocked when the pan‐Fpr antagonist Boc2 was co‐administered. Furthermore, administration of either Ac2‐26 or LXA4 2h after LPS challenge caused significant detachment of adherent leukocytes within 10 and 15 min, respectively. These novel results show both persistent and rapid leukocyte anti‐adhesive properties of FPR2/ALX agonists in endotoxaemia, and therefore implicate this system as a potential anti‐inflammatory target for the treatment of sepsis.