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(American Journal of Pathology. 2001;158:1969-1973.)
© 2001 American Society for Investigative Pathology

Short Communication

Involvement of the Receptor for Formylated Peptides in the in Vivo Anti-Migratory Actions of Annexin 1 and its Mimetics

Mauro Perretti^*, Stephen J. Getting^*, Egle Solito, Philip M. Murphy and Ji-Liang Gao

From The William Harvey Research Institute,^*
St. Bartholomew’s and The Royal London School of Medicine and Dentistry, London, United Kingdom; the Department of Neuroendocrinology,
Imperial College School of Medicine, London, United Kingdom; and the Laboratory of Host Defenses,
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland

An innovative avenue for anti-inflammatory therapy is inhibition of neutrophil extravasation by potentiating the action of endogenous anti-inflammatory mediators. The glucocorticoid-inducible protein annexin 1 and derived peptides are effective in inhibiting neutrophil extravasation. Here we tested the hypothesis that an interaction with the receptor for formylated peptide (FPR), so far reported only in vitro, could be the mechanism for this in vivo action. In a model of mouse peritonitis, FPR antagonists abrogated the anti-migratory effects of peptides Ac2-26 and Ac2-12, with a partial reduction in annexin 1 effects. A similar result was obtained in FPR (knock-out) KO mice. Binding of annexin 1 to circulating leukocytes was reduced (>50%) in FPR KO mice. In vitro, annexin binding to peritoneal macrophages was also markedly reduced in FPR KO mice. Finally, evidence of direct annexin 1 binding to murine FPR was obtained with HEK-293 cells transfected with the receptor. Overall, these results indicate a functional role for FPR in the anti-migratory effect of annexin 1 and derived peptides.

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