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MRC Immunochemistry Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. tony.day@bioch.ox.ac.uk
Production of the glycosaminoglycan hyaluronan is increased at sites of inflammation, often correlating with the accumulation of leukocytes. Mounting evidence suggests that this polysaccharide can be organized into a wide variety of molecular architectures by its association with specific binding proteins, leading to the formation of fibrils and cable-like structures involving a large number of hyaluronan chains. We propose that hyaluronan cross-linking is part of a protective mechanism, promoting adhesion of leukocytes to the hyaluronan complexes rather than enabling contact with inflammation-promoting receptors on the underlying tissues. Leukocytes are thus maintained in a non-activated state by appropriate receptor clustering or receptor co-engagement. Additionally, hyaluronan networks might serve as scaffolds to prevent the loss of extracellular matrix components during inflammation and to sequester proinflammatory mediators.
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