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
Sequestration of extracellular hemoglobin within a haptoglobin complex decreases its hypertensive and oxidative effects in dogs and guinea pigs
Felicitas S. Boretti, … , Abdu I. Alayash, Dominik J. Schaer
Felicitas S. Boretti, … , Abdu I. Alayash, Dominik J. Schaer
Published July 20, 2009
Citation Information: J Clin Invest. 2009;119(8):2271-2280. https://doi.org/10.1172/JCI39115.
View: Text | PDF
Research Article Article has an altmetric score of 3

Sequestration of extracellular hemoglobin within a haptoglobin complex decreases its hypertensive and oxidative effects in dogs and guinea pigs

  • Text
  • PDF
Abstract

Release of hemoglobin (Hb) into the circulation is a central pathophysiologic event that contributes to morbidity and mortality in chronic hemolytic anemias and severe malaria. These toxicities arise from Hb-mediated vasoactivity, possibly due to NO scavenging and localized tissue oxidative processes. Currently, there is no established treatment that targets circulating extracellular Hb. Here, we assessed the role of haptoglobin (Hp), the primary scavenger of Hb in the circulation, in limiting the toxicity of cell-free Hb infusion. Using a canine model, we found that glucocorticoid stimulation of endogenous Hp synthesis prevented Hb-induced hemodynamic responses. Furthermore, guinea pigs administered exogenous Hp displayed decreased Hb-induced hypertension and oxidative toxicity to extravascular environments, such as the proximal tubules of the kidney. The ability of Hp to both attenuate hypertensive responses during Hb exposure and prevent peroxidative toxicity in extravascular compartments was dependent on Hb-Hp complex formation, which likely acts through sequestration of Hb rather than modulation of its NO- and O2-binding characteristics. Our data therefore suggest that therapies involving supplementation of endogenous Hb scavengers may be able to treat complications of acute and chronic hemolysis, as well as counter the adverse effects associated with Hb-based oxygen therapeutics.

Authors

Felicitas S. Boretti, Paul W. Buehler, Felice D’Agnillo, Katharina Kluge, Tony Glaus, Omer I. Butt, Yiping Jia, Jeroen Goede, Claudia P. Pereira, Marco Maggiorini, Gabriele Schoedon, Abdu I. Alayash, Dominik J. Schaer

×

Figure 5

Absence of high-affinity Hb-Hp interactions with αα–cross-linked Hb in vivo.

Options: View larger image (or click on image) Download as PowerPoint
Absence of high-affinity Hb-Hp interactions with αα–cross-linked Hb in v...
(A) Representative chromatograms of αα–cross-linked Hb (αα-DBBF) in plasma from prednisone-treated dogs (blue line), the Hb-Hp complex in plasma from prednisone-treated dogs (red line), Hb and the Hb-Hp complex in plasma from control dogs (solid pink), and standard noninfused Hb (black dashed line). (B) Size exclusion chromatographs of plasma over a time course following αα–cross-linked Hb administration to prednisone-treated dogs. The red dotted line represents the chromatograph of heterodimeric Hb standard eluting similarly to αα–cross-linked Hb in the plasma of prednisone-treated (high Hp) dogs. No large-molecular-size protein complex containing heme could be detected at any time point.

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

Sign up for email alerts

Referenced in 1 Wikipedia pages
99 readers on Mendeley
See more details