Alginate enhances Toll-like receptor 4-mediated phagocytosis by murine RAW264.7 macrophages

Alginate is a naturally acidic polysaccharide consisting alternately of β-d-mannuronic acid and α-l-guluronic acid with 1, 4-glycosidic linkages and is derived from brown seaweeds. Herein, the effect of alginate on the promotion of macrophage phagocytosis and the corresponding molecular mechanisms were investigated in murine RAW264.7 cells. Alginate could enhance the intracellular phagocytosis of gold nanoparticles (AuNPs), fluorescent microspheres and immunoglobulin G (IgG)-opsonized Staphylococcus aureus (S. aureus). Moreover, alginate increased Toll-like receptor 4 (TLR4) expression and activated the Akt/nuclear factor-κB (NF-κB) and p38 mitogen-activated protein kinase (MAPK) signalling pathways. Alginate-promoted phagocytosis was suppressed by the addition of inhibitors of TLR4, NF-κB and p38 MAPK and by TLR4 gene knockdown, indicating the involvement of these key components. This work is the first to propose that alginate promotes phagocytosis via upregulating TLR4 expression and stimulating the Akt/NF-κB and p38 MAPK signalling pathways, which may contribute to the capacity of alginate to activate macrophages.