The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 15 September 2003. doi:10.1084/jem.20030374
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 500K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Strey, C. W.
Right arrow Articles by Lambris, J. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Strey, C. W.
Right arrow Articles by Lambris, J. D.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© Rockefeller University Press, 0022-1007/2003/9/913 $5.00
The Journal of Experimental Medicine, Volume 198, Number 6, 913-923

The Proinflammatory Mediators C3a and C5a Are Essential for Liver Regeneration

Christoph W. Strey1, Maciej Markiewski1, Dimitrios Mastellos1, Ruxandra Tudoran1, Lynn A. Spruce1, Linda E. Greenbaum2 and John D. Lambris1

1 Protein Chemistry Laboratory, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104
2 Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104

Address correspondence to John D. Lambris, Dept. of Pathology and Laboratory Medicine, Protein Chemistry Laboratory, University of Pennsylvania, 401 Stellar Chance/Curie Blvd., Philadelphia, PA 19104. Phone: (215) 746-5765; Fax: (215) 573-8738; email: lambris{at}mail.med.upenn.edu

Complement has been implicated in liver repair after toxic injury. Here, we demonstrate that complement components are essential for liver regeneration, and mediate their effect by interacting with key signaling networks that promote hepatocyte proliferation. C3- or C5-deficient mice exhibited high mortality, parenchymal damage, and impaired liver regeneration after partial hepatectomy. Mice with dual C3 and C5 deficiency had a more exacerbated phenotype that was reversed by combined C3a and C5a reconstitution. Interception of C5a receptor signaling resulted in suppression of IL-6/TNF{alpha} induction and lack of C3 and C5a receptor stimulation attenuated nuclear factor–{kappa}B/STAT-3 activation after hepatectomy. These data indicate that C3a and C5a, two potent inflammatory mediators of the innate immune response, contribute essentially to the early priming stages of hepatocyte regeneration.

Key Words: complement • anaphylatoxins • NF-{kappa}B • STAT-3 • IL-6


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS