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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
Statement of
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.
RMID: 0020100744
DOI: 10.4049/jimmunol.1000119
Appears in Collections:Molecular and Biomedical Science publications

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