Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on September 1, 2006

Published online before print June 22, 2006
This Article
Right arrow Full Text (Reprint (PDF))
Right arrow All Versions of this Article:
jlb.0306178v1
80/3/521    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cross, A.
Right arrow Articles by Moots, R. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cross, A.
Right arrow Articles by Moots, R. J.
© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0306178

Received for publication March 7, 2006.
Revised April 25, 2006.
Accepted for publication May 3, 2006.

Article

Neutrophil apoptosis in rheumatoid arthritis is regulated by local oxygen tensions within joints

Andrew Cross , Theresa Barnes , Roger C. Bucknall , Steven W. Edwards @, and Robert J. Moots

School of Biological Sciences and Department of Medicine, University of Liverpool, United Kingdom

@ To whom correspondence should be addressed. E-mail: S.W.Edwards{at}liv.ac.uk.


  Abstract

Neutrophils are normally short-lived cells and die by apoptosis, but when recruited into tissues, their apoptosis is delayed, and they survive for much longer time periods. In inflammatory diseases, such as rheumatoid arthritis (RA), this delayed apoptosis may lead to increased tissue damage and a failure of the inflammation to resolve. However, there are conflicting reports in the literature as to whether neutrophil apoptosis is delayed or accelerated in rheumatoid joints. In this report, we show that neutrophils isolated from the synovial fluid (SF) of patients with RA show accelerated rates of apoptosis when incubated ex vivo and that SF, despite containing a variety of antiapoptotic cytokines, is proapoptotic. Paradoxically, levels of the key neutrophil survival protein Mcl-1 are elevated in freshly isolated SF neutrophils compared with matched peripheral blood samples from the same patients, indicating that delayed neutrophil apoptosis has been signaled in vivo as the cells enter the joints. However, when SF was added to neutrophils and incubated under hypoxia (1% O2), conditions known to exist in vivo within joints, the SF was antiapoptotic. These data reveal that the rheumatoid synovial joint contains a complex mixture of pro- and antiapoptotic factors and that the low, local oxygen tensions that exist within these joints can exert profound effects on neutrophil survival. These experiments also highlight the importance of performing in vitro experiments under laboratory conditions that closely mimic those that occur in vivo; otherwise, misleading conclusions may be drawn.

Key Words: Mcl-1 • Bax • inflammation • hypoxia




This article has been cited by other articles:


Home page
 BloodHome page
A. Cross, R. J. Moots, and S. W. Edwards
The dual effects of TNF{alpha} on neutrophil apoptosis are mediated via differential effects on expression of Mcl-1 and Bfl-1
Blood, January 15, 2008; 111(2): 878 - 884.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
D. M. Cooper, S. Radom-Aizik, C. Schwindt, and F. Zaldivar Jr.
Dangerous exercise: lessons learned from dysregulated inflammatory responses to physical activity
J Appl Physiol, August 1, 2007; 103(2): 700 - 709.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Copyright © 2006 by the Society for Leukocyte Biology.