Differential effects of polysulfated polysaccharide on experimental encephalomyelitis, proliferation of autoimmune T cells, and inhibition of heparanase activity.
The extravasation of activated T lymphocytes through blood vessel walls and their migration to inflammatory loci are associated with secretion of extracellular matrix (ECM)-degrading enzymes, such as heparanase, which degrades heparan sulfate (HS) moieties of the ECM. The HS-degrading activity of heparanase was found to be inhibited by HS and heparin. Since induction of experimental autoimmune encephalomyelitis (EAE) requires extravasation and migration of autoimmune T cells, degradation of ECM by heparanase is expected to be involved in induction of the disease. Herein, we examined whether laminarin sulfate, a polysulfated polysaccharide (PSS) isolated from the cell walls of seaweeds and subjected to chemical sulfation, could inhibit ECM degradation by mammalian heparanase, and could prevent EAE. PSS was a more potent inhibitor of heparanase- mediated degradation of ECM than heparin. In-vivo, PSS, injected once a week, inhibited the severity of actively-induced EAE in rats. However, inhibition of EAE was not due to an overall suppression of autoimmune T cells, since PSS enhanced the proliferation of myelin basic protein (MBP)-specific, encephalitogenic T cells. PSS-activated autoimmune T cells, but not MBP-activated cells, failed to induce EAE in recipient rats. Moreover, rats injected with PSS-activated T cells were resistant to induction of EAE by anti- MBP CD4+ T cells. Thus, PSS may have potential clinical applications in the treatment of autoimmune diseases.[1]References
- Differential effects of polysulfated polysaccharide on experimental encephalomyelitis, proliferation of autoimmune T cells, and inhibition of heparanase activity. Hershkoviz, R., Mor, F., Miao, H.Q., Vlodavsky, I., Lider, O. J. Autoimmun. (1995) [Pubmed]
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