Modulation of immune cell activity is crucial in cancer immunotherapy as well as immune disease treatments. In particular, the antigen presenting cells (e.g., macrophage and dendritic cell) are major target cells in those therapies, because they play an important role in altering tumor microenvironment and to cancer vaccination. For example, conversion of tumor-associated macrophage phenotype (M2 to M1) is induced to inhibit tumor growth and the artificially activated dendritic cells are delivered to the patients for promoting anticancer adaptive immune processes. The antigen presenting cell activation or polarization is generally induced via treatment of immunomodulator (e.g., lipopolysaccharide). However, conventional immunomodulators have potential toxicity and might cause severe inflammatory response of patients. The water extract of root bark of Ulmus davidiana var. japonica has been traditionally used in herbal medicine for inflammatory disease treatment. Recently, the major component of the water extract is a pectic polysaccharide. In this work, we characterized the pectin from U. davidiana (UDP) and evaluated its immunomodulatory effect. Monosaccharide analysis indicated that UDP mainly consisted of homogalacturonan and rhamnogalacturonan region with galactose branches. To reduce the viscosity of the UDP solution, the ultrasonication was conducted, resulting in a decrease in molecular weight. Regardless of molecular weight, the UDP caused activation of macrophage. Specifically, the M0 macrophages were polarized to M1 phenotype by 100 μg/mL of UDP treatment. The UDP was modified with methacrylic anhydride for crosslinking. The UDP-methacrylate (UDPMA) formed a bulk hydrogel via short UV irradiation (10 s) in the presence of photoinitiator. Subsequently, the bulk gel was ground using a homogenizer, resulting in microgel formation and the microgel size was ~2 μm in diameter. The UDP microgels were successfully internalized by macrophages and dendritic cells, causing phagocyte activation. Especially, the internalized UDP microgels led to maturation of dendritic cells with relatively low inflammatory cytokine expressions compared with lipopolysaccharide. These findings indicated that the UDP is a promising candidate as a novel immunomodulator.

Immune activity of pectin from Ulmus davidiana var. japonica to macrophages and dendritic cells

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