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TheScientificWorldJOURNAL
Volume 6 (2006), Pages 1375-1384
http://dx.doi.org/10.1100/tsw.2006.247
Research Article

Antiflammin-2 Activates the Human Formyl-Peptide Receptor Like 1

1William Harvey Research Institute, Charterhouse Square, London EC1M 6BQ, UK
2Division of Neuroscience and Mental Health Imperial College London Hammersmith Hospital Campus, London W12 0NN, UK

Received 29 September 2006; Revised 16 October 2006; Accepted 17 October 2006

Academic Editor: John L. Wallace

Copyright © 2006 Ahmad M. Kamal et al.

Abstract

The anti-inflammatory actions of the nonapeptide antiflammin-2, identified by homology with uteroglobin and annexin-A1 sequences, have been described in some detail, yet its mechanisms of action remain elusive. Since recent data indicate an involvement of the formyl peptide receptor (FPR)-like 1 (or FPRL-1) in the effects of annexin-A1, we have tested here the effect of antiflammin-2 with respect to this receptor family. Using HEK-293 cells expressing either human FPR and FPRL-1, and an annexin-A1 peptide as tracer ([125I-Tyr]-Ac2-26), we found that antiflammin-2 competed for binding only at FPRL-1, and not FPR, with an approximate EC50 of 1 μM. In line with data produced for the full-length protein, genuine receptor activation by antiflammin-2 was confirmed by rapid phosphorylation of extracellular-regulated kinase 1 and 2. Finally, study of the neutrophil interaction with activated endothelium under flow demonstrated an inhibitory effect of antiflammin-2, thus providing functional support to a role for the antiflammin-2/FPRL-1 anti-inflammatory axis.