help button home button Am J Pathol JNCI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
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 Farrar, C. A.
Right arrow Articles by Zhou, W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Farrar, C. A.
Right arrow Articles by Zhou, W.
(American Journal of Pathology. 2004;164:133-141.)
© 2004 American Society for Investigative Pathology

Independent Pathways of P-Selectin and Complement-Mediated Renal Ischemia/Reperfusion Injury

Conrad A. Farrar*, Yi Wang{dagger}, Steven H. Sacks* and Wuding Zhou*

From the Department of Nephrology and Transplantation,* Guy’s Hospital, London, United Kingdom; and Alexion Pharmaceuticals,{dagger} New Haven, Connecticut

Evidence from in vitro studies indicates that complement activation regulates the expression of P-selectin on endothelial cells. This suggests that in disorders such as ischemia/reperfusion injury, in which both complement and P-selectin have been shown to play a role, complement activation is a primary event and the effects of P-selectin are secondary. To test this hypothesis in vivo, we examined a mouse kidney model of ischemia/reperfusion injury. Surprisingly, the time course and extent of expression of P-selectin was unaltered in C3-deficient mice compared with wild-type mice, in which there was rapid but transient up-regulation of P-selectin on capillary walls and slower accumulation of complement split product on the tubular epithelium. In addition, treatment with anti-P-selectin antibody to reduce the neutrophil-mediated reperfusion damage was equally effective in the absence of C3. These data imply that complement and P-selectin-mediated pathways of renal reperfusion injury are mutually independent, a conclusion that is possibly explained by the differences in the location and time kinetics of complement activation and P-selectin expression. We conclude that in vivo interaction between complement and P-selectin is limited because of time and spatial considerations. Consequently, complement and P-selectin pose distinct targets for therapy.




This article has been cited by other articles:


Home page
 J. Immunol.Home page
C. Atkinson, H. Zhu, F. Qiao, J. C. Varela, J. Yu, H. Song, M. S. Kindy, and S. Tomlinson
Complement-Dependent P-Selectin Expression and Injury following Ischemic Stroke
J. Immunol., November 15, 2006; 177(10): 7266 - 7274.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
H. Patel, R. A.G. Smith, S. H. Sacks, and W. Zhou
Therapeutic Strategy with a Membrane-Localizing Complement Regulator to Increase the Number of Usable Donor Organs after Prolonged Cold Storage
J. Am. Soc. Nephrol., April 1, 2006; 17(4): 1102 - 1111.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
C. A. Farrar, W. Zhou, T. Lin, and S. H. Sacks
Local extravascular pool of C3 is a determinant of postischemic acute renal failure
FASEB J, February 1, 2006; 20(2): 217 - 226.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
M. L. Kielar, R. John, M. Bennett, J. A. Richardson, J. M. Shelton, L. Chen, D. R. Jeyarajah, X. J. Zhou, H. Zhou, B. Chiquett, et al.
Maladaptive Role of IL-6 in Ischemic Acute Renal Failure
J. Am. Soc. Nephrol., November 1, 2005; 16(11): 3315 - 3325.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2004 by the American Society for Investigative Pathology.