American Society of Hirudotherapy

Oversulfated chondroitin sulfate binds to chemokines and inhibits stromal cell-derived factor-1 mediated signaling in activated T cells

Research article published in PloS one (2014)

Last Updated: June 18, 2026Reviewed by: ASH Editorial Board
Research article — evidence reviewArticle reference
Evidence: Research reportDrug DevelopmentSafety & Infection ControlZhou ZH et al. · PloS one, 2014

Abstract

Oversulfated chondroitin sulfate (OSCS), a member of the glycosaminoglycan (GAG) family, was a contaminant in heparin that was linked to the 2008 heparin adverse events in the US. Because of its highly negative charge, OSCS can interact with many components of the contact and immune systems. We have previously demonstrated that OSCS inhibited the complement classical pathway by binding C1 inhibitor and potentiating its interaction with C1s. In the present study, by using surface plasmon resonance, we found OSCS interacts with T cell chemokines that can impact adaptive immunity. The binding of OSCS to stromal cell-derived factor-1 (SDF-1) chemokines, SDF-1α and SDF-1β, caused a significant change in the secondary structures of these chemokines as detected by far-ultraviolet circular dichroism spectra analysis. Functionally, OSCS binding profoundly inhibited SDF-1-induced calcium mobilization and T cell chemotaxis. Imaging flow cytometry revealed T cell morphological changes mediated by SDF-1α were completely blocked by OSCS. We conclude that the OSCS, a past contaminant in heparin, has broad interactions with the components of the human immune system beyond the contact and complement systems, and that may explain, in part, prior OSCS-related adverse events, while suggesting potentially useful therapeutic applications for related GAGs in the control of inflammation.

Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.

Publication typeJournal ArticleResearch Support, U.S. Gov't, P.H.S.
Indexed MeSH termsCalcium SignalingCell ShapeChemokine CXCL12ChemotaxisChondroitin SulfatesGlycosaminoglycansHumansLymphocyte ActivationProtein Structure, SecondarySignal TransductionT-Lymphocytes

Summary

Oversulfated chondroitin sulfate (OSCS), a member of the glycosaminoglycan (GAG) family, was a contaminant in heparin that was linked to the 2008 heparin adverse events in the US.

Why This Matters for Hirudotherapy

This study demonstrates that oversulfated chondroitin sulfate (OSCS), a past contaminant in heparin, binds to T cell chemokines and significantly inhibits stromal cell-derived factor-1 mediated signaling, calcium mobilization, and morphological changes in T cells. The research investigates the immunological impacts and signaling pathways affected by this contaminant, concluding that OSCS has broad interactions with components of the human immune system beyond the contact and complement systems. The study has no involvement of leeches, hirudotherapy, or any leech-derived compounds. Therefore, its relevance to the American Society of Hirudotherapy is entirely absent, dealing exclusively with human immunology and the adverse events associated with a pharmaceutical contaminant.

Citation

Oversulfated chondroitin sulfate binds to chemokines and inhibits stromal cell-derived factor-1 mediated signaling in activated T cells

Zhou ZH et al. · PloS one, 2014

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