Gao J J, Zuvanich E G, Xue Q, Horn D L, Silverstein R, Morrison D C
Department of Microbiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
J Immunol. 1999 Oct 15;163(8):4095-9.
LPS is well recognized for its potent capacity to activate mouse macrophages to produce NO, an important inflammatory mediator in innate host defense. We demonstrate here that, although inducing little NO alone, DNA from both Gram-negative and Gram-positive bacteria synergizes with subthreshold concentrations of LPS (0.3 ng/ml) to induce NO in cultures of RAW 264.7 macrophages. The effects of the DNA are mimicked by synthetic CpG-containing oligodeoxynucleotides but not by non-CpG-containing oligodeoxynucleotides. This synergistic activity is not inhibited by neutralizing Abs against IFN. Preincubation of macrophages with DNA for 8-24 h suppresses subsequent synergistic macrophage responses to DNA/LPS, whereas prolonged pretreatment with LPS enhances synergy. RT-PCR analysis indicates that the mRNA levels of the inducible NO synthase gene are also coordinately suppressed or induced. These findings indicate that temporally controlled, synergistic interactions exist between microbial DNA and LPS in the induction of macrophage NO via enhanced inducible NO synthase gene expression.
脂多糖（LPS）以其激活小鼠巨噬细胞产生一氧化氮（NO）的强大能力而闻名，NO是天然宿主防御中的一种重要炎症介质。我们在此证明，尽管单独诱导产生的NO很少，但革兰氏阴性菌和革兰氏阳性菌的DNA与亚阈值浓度的LPS（0.3 ng/ml）协同作用，可在RAW 264.7巨噬细胞培养物中诱导产生NO。DNA的作用可被含CpG的合成寡脱氧核苷酸模拟，但不能被不含CpG的寡脱氧核苷酸模拟。这种协同活性不受抗干扰素中和抗体的抑制。巨噬细胞与DNA预孵育8 - 24小时可抑制随后巨噬细胞对DNA/LPS的协同反应，而用LPS进行长时间预处理则增强协同作用。逆转录-聚合酶链反应（RT-PCR）分析表明，诱导型一氧化氮合酶基因的mRNA水平也受到协同抑制或诱导。这些发现表明，在通过增强诱导型一氧化氮合酶基因表达诱导巨噬细胞产生NO的过程中，微生物DNA和LPS之间存在时间上受控的协同相互作用。
