Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • 100th Anniversary of Insulin's Discovery (Jan 2021)
    • Hypoxia-inducible factors in disease pathophysiology and therapeutics (Oct 2020)
    • Latency in Infectious Disease (Jul 2020)
    • Immunotherapy in Hematological Cancers (Apr 2020)
    • Big Data's Future in Medicine (Feb 2020)
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • View all review series ...
  • Viewpoint
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
Altered renal tubular expression of the complement inhibitor Crry permits complement activation after ischemia/reperfusion
Joshua M. Thurman, … , Moshe Levi, V. Michael Holers
Joshua M. Thurman, … , Moshe Levi, V. Michael Holers
Published February 1, 2006
Citation Information: J Clin Invest. 2006;116(2):357-368. https://doi.org/10.1172/JCI24521.
View: Text | PDF
Research Article Nephrology

Altered renal tubular expression of the complement inhibitor Crry permits complement activation after ischemia/reperfusion

  • Text
  • PDF
Abstract

Ischemia/reperfusion (I/R) of several organs results in complement activation, but the kidney is unique in that activation after I/R occurs only via the alternative pathway. We hypothesized that selective activation of this pathway after renal I/R could occur either because of a loss of complement inhibition or from increased local synthesis of complement factors. We examined the relationship between renal complement activation after I/R and the levels and localization of intrinsic membrane complement inhibitors. We found that loss of polarity of complement receptor 1–related protein y (Crry) in the tubular epithelium preceded activation of the alternative pathway along the basolateral aspect of the tubular cells. Heterozygous gene-targeted mice that expressed lower amounts of Crry were more sensitive to ischemic injury. Furthermore, inhibition of Crry expressed by proximal tubular epithelial cells in vitro resulted in alternative pathway–mediated injury to the cells. Thus, altered expression of a complement inhibitor within the tubular epithelium appears to be a critical factor permitting activation of the alternative pathway of complement after I/R. Increased C3 mRNA and decreased factor H mRNA were also detected in the outer medulla after I/R, suggesting that altered synthesis of these factors might further contribute to complement activation in this location.

Authors

Joshua M. Thurman, Danica Ljubanović, Pamela A. Royer, Damian M. Kraus, Hector Molina, Nicholas P. Barry, Gregory Proctor, Moshe Levi, V. Michael Holers

×

Figure 1

Localization of membrane-bound complement inhibitors within the mouse kidney.

Options: View larger image (or click on image) Download as PowerPoint
Localization of membrane-bound complement inhibitors within the mouse ki...
Three different membrane-bound complement inhibitors are located within the mouse kidney. (A) Crry is expressed in the glomeruli (arrowhead) and in tubules. (B) Crry in the renal tubules is polarized to the basolateral aspect of the tubules. Inset: Dual staining for Crry (green) and type IV collagen (red) demonstrates that expression of Crry is adjacent to the tubular basement membrane. Staining with secondary antibody alone in unmanipulated kidneys (C) and kidneys subjected to ischemia and 2 hours of reperfusion (D) demonstrate the specificity of staining with the anti-Crry antibody. (E) CD59 and (F) DAF are also expressed in glomeruli (arrowheads). In addition, these inhibitors may be expressed in the small blood vessels (arrows), but not in tubules. Original magnification, ×200 (A and C–F); ×400 (B).
Follow JCI:
Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts