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Related Experiment Videos

TSG-6 modulates the interaction between hyaluronan and cell surface CD44.

Jayne Lesley1, István Gál, David J Mahoney

  • 1Molecular and Cell Biology Laboratory, The Salk Institute, San Diego, California 92186, USA.

The Journal of Biological Chemistry
|April 3, 2004
PubMed
Summary

Tumor necrosis factor-stimulated gene-6 (TSG-6) enhances hyaluronan binding to CD44 receptors on cells. This interaction is crucial for lymphocyte adhesion at inflammatory sites, influencing cell rolling and adhesion under flow conditions.

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Area of Science:

  • Immunology
  • Biochemistry
  • Cell Biology

Background:

  • CD44 receptor interactions with hyaluronan are critical for lymphocyte adhesion to endothelium at inflammatory sites.
  • TSG-6 is a protein expressed at sites of inflammation, suggesting a role in modulating these interactions.

Purpose of the Study:

  • To investigate how TSG-6 influences the binding of hyaluronan to CD44.
  • To determine the functional consequences of TSG-6 mediated modulation of hyaluronan-CD44 interactions under physiological flow conditions.

Main Methods:

  • Utilized full-length recombinant TSG-6 and its Link module domain (Link_TSG6) to preincubate with hyaluronan.
  • Assessed binding to CD44 on various cell types, including CD44-negative cells.
  • Performed flow chamber experiments to mimic post-capillary venule shear forces.

Related Experiment Videos

  • Conducted ligand competition assays and analyzed TSG-6 mutants with altered hyaluronan binding.
  • Main Results:

    • TSG-6 and Link_TSG6 enhanced or induced hyaluronan binding to CD44, effects blocked by CD44 antibodies and absent in CD44-negative cells.
    • TSG-6 preincubation increased lymphocyte rolling on hyaluronan substrates under flow conditions.
    • TSG-6-hyaluronan complexes were more potent inhibitors of cell adhesion than hyaluronan alone.
    • Mutants suggested involvement of residues outside the hyaluronan binding site in TSG-6's activity, potentially via cross-linked hyaluronan fibers and CD44 clustering.

    Conclusions:

    • TSG-6 significantly modulates hyaluronan binding to CD44, enhancing cell adhesion under inflammatory conditions.
    • TSG-6-induced cross-linking of hyaluronan may promote CD44 receptor clustering, increasing binding avidity.
    • These findings highlight the importance of TSG-6 in regulating CD44-mediated cellular activities at inflammatory sites.