The formyl-peptide receptor-like 1 (FPRL1), also known as lipoxin A4 receptor, is expressed primarily on monocytes and neutrophils. The roles for FPRL1 in inflammatory processes are poorly understood, but agonists appear to ameliorate inflammation. In this issue, Hecht et al. describe the evaluation of cardioprotection by the peptide CGEN-855A (TIPMFVPESTSKLQKFTSWFM-amide) that was developed as an FPRL1 agonist. Activity of the peptide was evaluated using radioligand binding. Cell impedance and calcium mobilization in stably transfected Chinese hamster ovary cells demonstrated agonist activity. Rodents were also used to evaluate the effect of CGEN-855A on polymorphonuclear neutrophil (PMN) infiltration into air pouches and following myocardial ischemia/reperfusion. In vivo, CGEN-855A inhibited PMN recruitment to inflamed air pouches in mice and heart in mice and rats, where it also protected against myocardial ischemia/reperfusion damage. The in vivo activity of CGEN-855A supports its further development as an agent for treatment of inflammatory diseases and ischemia/reperfusion inflammatory damage.
See article at J Pharmacol Exp Ther 2009, 328:426–434.
- The American Society for Pharmacology and Experimental Therapeutics