Fucoidans inhibit cellular responses to the chemokine IL-8 and the anaphylatoxin C5a better than heparin
S. Alban, K. Ehrig, I. Liewert (Kiel, Germany)
Time: 11:00 - 12:00
Objective: Heparins are known to exhibit anti-inflammatory and antimetastatic activities, however their application in inflammatory diseases and cancer is limited due their bleeding risk. Fucose-containing sulfated polysaccharides (fucoidans) from brown algae, which are currently considered promising candidates for health-supporting and medicinal applications, showed anti-inflammatory and antimetastatic activity in vivo as well, but considerably reduced anticoagulant effects. However, there is only limited knowledge about their mode of actions. Potential targets may be the chemokine interleukin 8 (IL-8) and the anaphylatoxin C5a, as they are closely linked to both inflammatory processes and tumor progression. In the present study, two structurally distinct fucoidans, SLSP from Saccharina latissimi and FVSP from Fucus vesiculosus, and UFH as reference were examined for their effects on IL-8- and C5a-induced reactions of polymorphonuclear neutrophils (PMN) as cell type critically involved in many inflammatory diseases.
Methods: The affinity of the test compounds to IL-8 and C5a was examined by competitive SPC-ELISA. PMN activation was determined by means of intracellular calcium release and Erk1/Erk2 phosphorylation. The IL-8- and C5a-induced PMN chemotaxis was assessed using modified Boyden chambers.
Results: Both fucoidans (SLSP > FVSP), but not UFH, displayed high affinity to IL-8 as well as C5a. Whereas UFH showed only moderate effects, the fucoidans (FVSP > SLSP) conc.-dependently reduced the Il-8- and C5a-induced intracellular calcium release. The conc.-dependent inhibition of Erk phosphorylation was more pronounced in IL-8- than in C5a-stimulated PMN. Similar to this discrepancy, the IL-8-induced chemotaxis was effectively inhibited by the fucoidans and up to 30% by UFH, whereas migration towards C5a was only reduced to 50% by the fucoidans and not at all by UFH. Strikingly, SLSP and FVSP differed in their inhibitory profile on the IL-8-induced chemotaxis with stronger inhibition by SLSP at <10µg/ml and a superior effect of FVSP at higher concentrations.
Conclusion: In conclusion, the two fucoidans showed to interfere with IL-8- and C5a-induced stimulation of PMN by binding to these activators. They proved to be considerably more active than UFH, however, their activity profiles differed. This suggests that further mechanisms may be involved in their inhibitory effects on PMN.