Comparative study of the immunomodulatory effects of different fucoidans from Saccharina japonica mediated by scavenger receptors on RAW 264.7 macrophages

Scavenger receptors (SRs) have been shown to participate in regulating the immune response of macrophages, and fucoidan from Fucus vesiculosus has been verified as a ligand of class A SRs (SR-A). However, the roles of SRs in the immunomodulatory activity of fucoidan from Saccharina japonica are not clear. Thus, we performed a comparative study of the immunomodulatory activities of six different fucoidans from S. japonica on RAW 264.7 macrophages, and the roles of SRs in the processes were studied. Six fucoidans (0.5 M FPS, 1 M FPS, 2 M FPS, 0.5 M DFPS, 1 M DFPS and 2 M FPS) had different molecular weights and chemical compositions. Griess reagent system, ELISA and RT-qPCR results showed that different fucoidans displayed different stimulation of macrophages to secrete NO, IL-6, IL-1β and TNF-α, as well as differences in the upregulation of their gene expressiones. Flow cytometric analysis of the protein expression level indicated the upregulation of TLR4 after treatment with all the fucoidans but different expressions of SRs. Furthermore, only 0.5 M DFPS and 1 M DFPS were confirmed to be ligands of SR-A through the competitive binding assay with Ac-LDL bound to the fluorescent probe DiI by flow cytometry. Our results revealed that fucoidans with low molecular weight and heterogeneity more easily bound to SRs and contributed to their immunomodulatory effects. This comparative study might promote the biological study of targeted SRs and the discovery of new pharmacological mechanisms of different fucoidans.