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Blood, 1 March 2006, Vol. 107, No. 5, pp. 2123-2130. Prepublished online as a Blood First Edition Paper on November 8, 2005; DOI 10.1182/blood-2005-08-3099. This Article Full Text (PDF) All Versions of this Article: 2005-08-3099v1 107/5/2123    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hayhoe, R. P Articles by Perretti, M. Search for Related Content PubMed PubMed Citation Articles by Hayhoe, R. P Articles by Perretti, M. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 2, 2005 Accepted October 18, 2005 Annexin 1 and its bioactive peptide inhibit neutrophil-endothelium interactions under flow: indication of distinct receptor involvement Richard P Hayhoe, Ahmad M Kamal, Egle Solito, Roderick J Flower, Dianne Cooper, and Mauro Perretti* Centre for Biochemical Pharmacology, The William Harvey Research Institute, London, United Kingdom Department of Cellular and Molecular Neuroscience, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, United Kingdom * Corresponding author; email: m.perretti{at}qmul.ac.uk. We have tested the effects of annexin 1 (ANXA1) and its N-terminal peptide Ac2-26 on PMN recruitment under flow. Differential effects of the full-length protein and its peptide were observed; ANXA1 inhibited firm adhesion of human PMN, whilst Ac2-26 significantly attenuated capture and rolling without effect on firm adhesion. Analysis of the effects of ANXA1 and Ac2-26 on PMN adhesion molecule expression supported the flow chamber results, with Ac2-26 but not ANXA1 causing L-selectin and PSGL-1 shedding. ANXA1 and its peptide act via the FPR family of receptors. This was corroborated using HEK-293 cells transfected with FPR or FPRL-1/ALX (the two members of this family expressed by human PMN). While Ac2-26 bound both FPR and FPRL-1/ALX, ANXA1 bound FPRL-1/ALX only. ANXA1 and Ac2-26 acted as genuine agonists; Ac2-26 binding led to ERK activation in both FPR and FPRL-1/ALX transfected cells while ANXA1 caused ERK activation only in cells transfected with FPRL-1/ALX. Finally blockade of FPRL-1/ALX with a neutralising monoclonal antibody was found to abrogate the effects of ANXA1 in the flow chamber but was without effect on Ac2-26-mediated inhibition of rolling. These findings demonstrate for the first time distinct mechanisms of action for ANXA1 and its N-terminal peptide Ac2-26. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Putting the brakes on neutrophils Charles N. Serhan and Nan Chiang Blood 2006 107: 1742-1743. [Full Text] [PDF] This article has been cited by other articles: N. Markovic, L. A. McCaig, J. Stephen, S. Mizuguchi, R. A. W. Veldhuizen, J. F. Lewis, and G. Cepinskas Mediators released from LPS-challenged lungs induce inflammatory responses in liver vascular endothelial cells and neutrophilic leukocytes Am J Physiol Gastrointest Liver Physiol, December 1, 2009; 297(6): G1066 - G1076. [Abstract] [Full Text] [PDF] S. McArthur, S. Yazid, H. Christian, R. 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Pathol., January 1, 2009; 174(1): 177 - 183. [Abstract] [Full Text] [PDF] J. Dalli, L. V. Norling, D. Renshaw, D. Cooper, K.-Y. Leung, and M. Perretti Annexin 1 mediates the rapid anti-inflammatory effects of neutrophil-derived microparticles Blood, September 15, 2008; 112(6): 2512 - 2519. [Abstract] [Full Text] [PDF] D. El Kebir, L. Jozsef, and J. G. Filep Opposing regulation of neutrophil apoptosis through the formyl peptide receptor-like 1/lipoxin A4 receptor: implications for resolution of inflammation J. Leukoc. Biol., September 1, 2008; 84(3): 600 - 606. [Abstract] [Full Text] [PDF] D. Cooper, L. V. Norling, and M. Perretti Novel insights into the inhibitory effects of Galectin-1 on neutrophil recruitment under flow J. Leukoc. Biol., June 1, 2008; 83(6): 1459 - 1466. [Abstract] [Full Text] [PDF] S. Yona, H.-H. Lin, P. Dri, J. Q. Davies, R. P. G. Hayhoe, S. M. Lewis, S. E. M. Heinsbroek, K. A. Brown, M. Perretti, J. Hamann, et al. 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