Korean mistletoe lectin (KML-IIU) and its subchains induce nitric oxide (NO) production in murine macrophage cells.
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-gamma, 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.
Kang
Tae Bong
TB
School of Food and Biosciences, Handong Global University, Pohang, 791-708, Korea.
Yoo
Yung Choon
YC
Lee
Kwan Hee
KH
Yoon
Ho Sup
HS
Her
Erk
E
Kim
Jong Bae
JB
Song
Seong Kyu
SK
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000276:immunology; D007113:Immunity, Innate / Q000187:drug effects; D007371:Interferon-gamma / Q000494:pharmacology; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D008264:Macrophages / Q000201:enzymology* / Q000276:immunology; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology; D028321:Plant Preparations / Q000494:pharmacology*; D010940:Plant Proteins / Q000494:pharmacology*; D054788:Ribosome Inactivating Proteins / Q000494:pharmacology*; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological / Q000494:pharmacology*
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; C090663:N(6)-(1-iminoethyl)lysine; D028321:Plant Preparations; D010940:Plant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; C488863:mistletoe lectin II; D009569:Nitric Oxide; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D054788:Ribosome Inactivating Proteins; D008239:Lysine; D019331:NG-Nitroarginine Methyl Ester