Korean mistletoe lectin (KML-IIU) and its subchains induce nitric oxide (NO) production in murine macrophage cells

Abstract

Synthesis of nitric oxide (NO) is one of the important effector functions of innate immune cells. Although

several reports have indicated mistletoe lectins induce immune cells to produce cytokines, studies regarding

the activities of the lectins in the production of NO have been very limited. Here, we report on the induction

of NO synthesis in a murine macrophage cell line, RAW264.7, by Korean mistletoe lectin (KML-IIU).

When the macrophage cells were treated with KML-IIU in the presence of a suboptimal concentration of

IFN-γ, NO production was induced in a concentration-dependent manner. Significantly higher levels of NO

were induced by subchains of the KML-IIU (A and B), which have lower toxicities, as compared to the

hololectin. Furthermore, expression of the inducible nitric oxide synthase (iNOS) gene was elevated in

accordance with the level of NO production. When the synthase was inhibited by iNOS inhibitors (L-NIL

and L-NAME), NO production was specifically reduced in a concentration-dependent manner. Our studies

demonstrate that the KML-IIU and its subchains induce NO production in murine macrophage cells via

activation of the iNOS gene expression, suggesting that the KML-IIU subchains may be used as an

immunomodulator to enhance the effector functions of innate immune cells.