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Involvement of the receptor for formylated peptides in the in vivo anti-migratory actions of annexin 1 and its mimetics

Perretti, Mauro and Getting, Stephen J. and Solito, Egle and Murphy, Philip M. and Gao, Ji-Liang (2001) Involvement of the receptor for formylated peptides in the in vivo anti-migratory actions of annexin 1 and its mimetics. American Journal of Pathology, 158 (6). pp. 1969-1973. ISSN 0002-9440

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Abstract

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.

Item Type:Article
Research Community:University of Westminster > Life Sciences, School of
ID Code:10851
Deposited On:18 Jul 2012 16:48
Last Modified:18 Jul 2012 16:48

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