Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • 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
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Collectin-11 detects stress-induced L-fucose pattern to trigger renal epithelial injury
Conrad A. Farrar, … , Wuding Zhou, Steven H. Sacks
Conrad A. Farrar, … , Wuding Zhou, Steven H. Sacks
Published April 18, 2016
Citation Information: J Clin Invest. 2016;126(5):1911-1925. https://doi.org/10.1172/JCI83000.
View: Text | PDF
Research Article Nephrology

Collectin-11 detects stress-induced L-fucose pattern to trigger renal epithelial injury

  • Text
  • PDF
Abstract

Physiochemical stress induces tissue injury as a result of the detection of abnormal molecular patterns by sensory molecules of the innate immune system. Here, we have described how the recently discovered C-type lectin collectin-11 (CL-11, also known as CL-K1 and encoded by COLEC11) recognizes an abnormal pattern of L-fucose on postischemic renal tubule cells and activates a destructive inflammatory response. We found that intrarenal expression of CL-11 rapidly increases in the postischemic period and colocalizes with complement deposited along the basolateral surface of the proximal renal tubule in association with L-fucose, the potential binding ligand for CL-11. Mice with either generalized or kidney-specific deficiency of CL-11 were strongly protected against loss of renal function and tubule injury due to reduced complement deposition. Ex vivo renal tubule cells showed a marked capacity for CL-11 binding that was induced by cell stress under hypoxic or hypothermic conditions and prevented by specific removal of L-fucose. Further analysis revealed that cell-bound CL-11 required the lectin complement pathway–associated protease MASP-2 to trigger complement deposition. Given these results, we conclude that lectin complement pathway activation triggered by ligand–CL-11 interaction in postischemic tissue is a potent source of acute kidney injury and is amenable to sugar-specific blockade.

Authors

Conrad A. Farrar, David Tran, Ke Li, Weiju Wu, Qi Peng, Wilhelm Schwaeble, Wuding Zhou, Steven H. Sacks

×

Figure 1

Acute-phase response of CL-11 and associated molecules in mouse kidney.

Options: View larger image (or click on image) Download as PowerPoint
Acute-phase response of CL-11 and associated molecules in mouse kidney.
...
Detection of CL-11 and potential ligand (L-fucose) and complement activation product (C3d) are shown in normal mouse kidney and injured kidney after 50 minutes of ischemia and up to 24 hours of reperfusion. (A) Agarose gel image demonstrating Colec11 mRNA expression in normal and ischemic kidney tissue, determined by semiquantitative RT-PCR. Colec11 appears as a 315-bp product, and Gapdh (453 bp) is included as an internal control. M, 100 bp DNA ladder. n = 2 mice/group. (B) Quantification of Colec11 mRNA expression in normal and ischemic kidney tissue by real-time quantitative RT-PCR (qRT-PCR) demonstrating upregulation of intrarenal Colec11 mRNA expression following ischemic insult. Each dot represents an individual mouse (n = 4 mice/group). ***P < 0.005, by 1-way ANOVA. (C) Representative immunofluorescence microscopic images of renal cortex showing particulate staining of CL-11 (red), linear peritubular staining of C3d (green), and a merged image of CL-11 and C3d in normal and ischemic kidney tissue (n = 4 mice/group). (D) Enlargement (original magnification, ×400) of white boxed area in panel C, with arrows showing coexpression of CL-11 and complement deposition (orange) along the basolateral border of renal tubular epithelium. (E) Representative fluorescence images of CL-11 (red), L-fucose (green), and a merged image of CL-11 and L-fucose in normal and ischemic kidney tissue (n = 6 mice/group) showing ischemia-related coexpression of CL-11 and L-fucose (orange) along the basolateral border of the tubules. Scale bars: 25 μm.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts