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Acceleration of human neutrophil apoptosis by TRAIL

Renshaw, S. A., Parmar, J. S., Singleton, V., Rowe, S. J., Dockrell, D. H., Dower, S. K., Bingle, C. D., Chilvers, E. R. and Whyte, M. K. B. (2003) Acceleration of human neutrophil apoptosis by TRAIL. The Journal of Immunology, 170 (2). pp. 1027-1033. ISSN 0022-1767

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Neutrophil granulocytes have a short lifespan, with their survival limited by a constitutive program of apoptosis. Acceleration of neutrophil apoptosis following ligation of the Fas death receptor is well-documented and TNF-alpha also has a transient proapoptotic effect. We have studied the role of the death receptor ligand TRAIL in human neutrophils. We identified the presence of mRNAs for TRAIL, TRAIL-R2, and TRAIL-R3, and cell surface expression of TRAIL-R2 and -R3 in neutrophil populations. Neutrophil apoptosis is specifically accelerated by exposure to a leucine zipper-tagged form of TRAIL, which mimics cell surface TRAIL. Using blocking Abs to TRAIL receptors, specifically TRAIL-R2, and a TRAIL-R1:FcR fusion protein, we have excluded a role for TRAIL in regulating constitutive neutrophil apoptosis. No additional proapoptotic effect of leucine zipper TRAIL was identified following TRAIL treatment of neutrophils in the presence of gliotoxin, an inhibitor of NF-kappaB, suggesting TRAIL does not activate NF-kappaB in human neutrophils. TRAIL treatment of human neutrophils did not induce a chemotactic response. The susceptibility of neutrophils to TRAIL-mediated apoptosis suggests a role for TRAIL in the regulation of inflammation and may provide a mechanism for clearance of neutrophils from sites of inflammation.

Item Type: Article
Institution: The University of Sheffield
Academic Units: The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine (Sheffield)
Depositing User: Miss Anthea Tucker
Date Deposited: 29 Mar 2012 09:45
Last Modified: 29 Mar 2012 09:45
Published Version: http://www.jimmunol.org/content/170/2/1027.long
Status: Published
Publisher: American Association of Immunologists
Related URLs:
URI: http://eprints.whiterose.ac.uk/id/eprint/43820

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