Abstract
Fucoidans are natural polysaccharides mainly consisting of sulfated α-L-fucopyranose. A wide range of biological activities has been attributed to fucoidans. However, their immunostimulatory role with respect to structure-activity relationships is still under debate. To address this question, hyposulfated (hypoS), deacetylated (deAc), and both hyposulfated and deacetylated (hypoSdeAc) derivatives of native Fucus evanescens fucoidan were used to stimulate bone marrow–derived dendritic cells (BMDCs) and bone marrow–derived macrophages (BMMs).
Native fucoidan induced proinflammatory cytokines (IL-1β, IL-6, IL-12, TNF-α) by murine BMDCs and BMMs. Hyposulfation led to a markedly reduced cytokine secretion by BMDCs (35% to 70% reduction compared to native fucoidan) and BMMs (60% to 90% reduction). Cytokine release was also largely decreased by deacetylation (50% to 60% reduction in BMDCs, 50% to 70% reduction in BMMs compared to native fucoidan). In BMDCs and BMMs stimulated with hypoSdeAc, cytokine production was almost completely abolished. In conclusion, our results indicate the importance of sulfate/acetyl groups for the immunostimulatory activity of fucoidans.
ACKNOWLEDGEMENTS
This work was financially supported by the Far-East Branch of the Russian Academy of Science (project no. 09-I-P21-03), the Russian Foundation for Basic Research (project no. 09-04-00761-a), and the program “Molecular and Cellular Biology” for Basic Research of the Presidium of the Russian Academy of Science. Funding by the Max Planck Society and by the German Federal Ministry of Education and Research (BMBF, Fkz. 0315446 to B.L.) is also gratefully acknowledged. S.R.K. gratefully thanks the German Academic Exchange Service (DAAD) for granting him a research fellowship in Germany.