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https://hdl.handle.net/2440/61015
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Type: | Journal article |
Title: | A proinflammatory role for proteolytically cleaved annexin A1 in neutrophil transendothelial migration |
Author: | Williams, S. Milne, I. Bagley, C. Gamble, J. Vadas, M. Pitson, S. Khew-Goodall, Y. |
Citation: | Journal of Immunology, 2010; 185(5):3057-3063 |
Publisher: | Amer Assoc Immunologists |
Issue Date: | 2010 |
ISSN: | 0022-1767 1550-6606 |
Statement of Responsibility: | Samantha L. Williams, Ian R. Milne, Christopher J. Bagley, Jennifer R. Gamble, Mathew A. Vadas, Stuart M. Pitson, and Yeesim Khew-Goodall |
Abstract: | Neutrophil extravasation, a critical component of innate immunity must be tightly regulated to prevent inadvertent or prolonged inflammation and subsequent tissue damage. We have shown previously that endothelial ERK1/2 signaling essential for neutrophil transendothelial migration is induced by a soluble factor produced by activated neutrophils. In this study, we demonstrate that the soluble neutrophil factor is a truncated form of annexin A1 (AnxA1) that can be generated by calpain 1 cleavage of the N terminus, thus identifying a novel proinflammatory function to AnxA1. In contrast, neither the full-length protein nor the N-terminal 26 aa peptide, previously shown to be antiinflammatory, were able to activate Erk. Our data suggest that two different fragments of AnxA1 have opposing functions in inflammation. We also provide evidence that C-terminal AnxA1 functions by increasing ICAM1 clustering around adherent neutrophils to anchor them to the endothelium and promote transmigration through the transcellular route. |
Keywords: | Endothelium, Vascular Neutrophils Cell Line Humans Calpain Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Peptide Fragments Annexin A1 Inflammation Mediators Cell Movement Neutrophil Activation Amino Acid Sequence Molecular Sequence Data |
Rights: | Copyright © 2010 by The American Association of Immunologists, Inc. |
DOI: | 10.4049/jimmunol.1000119 |
Published version: | http://dx.doi.org/10.4049/jimmunol.1000119 |
Appears in Collections: | Aurora harvest 5 Molecular and Biomedical Science publications |
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