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@article{Lesley2004,
abstract = {Interactions between CD44 and hyaluronan are implicated in the primary adhesion of lymphocytes to endothelium at inflammatory locations. Here we show that preincubation of hyaluronan with full-length recombinant TSG-6 or its Link module domain (Link{\_}TSG6) enhances or induces the binding of hyaluronan to cell surface CD44 on constitutive and inducible cell backgrounds, respectively. These effects are blocked by CD44-specific antibodies and are absent in CD44-negative cells. Enhancement of CD44-mediated interactions of lymphoid cells with hyaluronan by TSG-6 proteins was seen under conditions of flow at shear forces that occur in post-capillary venules. Increases in the number of rolling cells were observed on substrates comprising TSG-6-hyaluronan complexes as compared with a substrate containing hyaluronan alone. In ligand competition experiments, cell surface-bound TSG-6-hyaluronan complexes were more potent than hyaluronan alone in inhibiting cell adhesion to immobilized hyaluronan. Link{\_}TSG6 mutants with impaired hyaluronan binding function had a reduced ability to modulate ligand binding by cell surface CD44. However, some mutants that exhibited close to wild-type hyaluronan binding were found to have either reduced or increased activity, suggesting that some amino acid residues outside of the hyaluronan binding site might be involved in protein self-association, potentially leading to the formation of cross-linked hyaluronan fibers. In turn, cross-linked hyaluronan could increase the binding avidity of CD44 by inducing receptor clustering. The ability of TSG-6 to modulate the interaction of hyaluronan with CD44 has important implications for CD44-mediated cell activity at sites of inflammation, where TSG-6 is expressed.},
author = {Lesley, Jayne and Gal, I. and Mahoney, David J and Cordell, Martin R and Rugg, Marilyn S and Hyman, Robert and Day, Anthony J and Mikecz, Katalin},
doi = {10.1074/jbc.M313319200},
file = {:media/Daten/Dokumente/Universit{\"{a}}t/Wissenschaftliche Projekte/Bib/2004/Lesley et al. - TSG-6 Modulates the Interaction between Hyaluronan and Cell Surface CD44.pdf:pdf},
institution = {Molecular and Cell Biology Laboratory, The Salk Institute, San Diego, California 92186, USA.},
issn = {0021-9258},
journal = {Journal of Biological Chemistry},
keywords = {Animals,Antigens,CD44,CD44: metabolism,Cell Adhesion,Cell Adhesion Molecule,Cell Adhesion Molecules,Cell Adhesion Molecules: physiology,Cell Line,Cell Movement,Hyaluronic Acid,Hyaluronic Acid: metabolism,Inbred AKR,Mice,Tumor,metabolism,physiology},
month = {jun},
number = {24},
pages = {25745--25754},
pmid = {15060082},
title = {{TSG-6 Modulates the Interaction between Hyaluronan and Cell Surface CD44}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15060082 http://dx.doi.org/10.1074/jbc.M313319200 http://www.jbc.org/cgi/doi/10.1074/jbc.M313319200},
volume = {279},
year = {2004}
}