Immunostimulatory Activity of Fucoidan from the Brown Alga Fucus evanescens: Role of Sulfates and Acetates

Fucoidans are natural polysaccharides mainly consisting of sulfated alpha-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-1 beta, IL-6, IL-12, TNF-alpha) 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.