Pfaff A W, Schulz-Key H, Soboslay P T, Geiger S M, Hoffmann W H
Institute for Tropical Medicine, University of Tübingen, Germany.
Parasite Immunol. 2000 Aug;22(8):397-405. doi: 10.1046/j.1365-3024.2000.00317.x.
Nitric oxide (NO) has been shown to be an important effector mechanism in the defence against various pathogens, including filariae. The production of NO, as well as H2O2, is induced by the Th1 cytokine IFN-gamma. Therefore, the microfilariae (mf) of filarial nematodes, which are known to elicit the release of IFN-gamma, may be a target of NO release. In this study, we found that mf of the filarial species Litomosoides sigmodontis were resistant to the attack of H2O2, but vulnerable to NO exposure in vitro by a chemical NO donor, as well as activated macrophages. Adult worms were considerably less affected by exposure to NO. In-vivo production of NO following injection of mf, in this and previous studies, suggested a central role in the defence to filariae. However, neither pharmaceutical inhibition of nitric oxide synthesis, nor genetic knockout of the gene for inducible nitric oxide synthase (iNOS), abrogated resistance to circulating mf in mice. Interestingly, however, iNOS-KO mice showed higher interleukin (IL)-2 responses and lower IL-10 production, compared to their wild-type counterparts. In conclusion, despite its effectiveness in vitro and the observed production of NO by ex vivo cells following infection, nitric oxide seems not to be an important factor in elimination of mf of L. sigmodontis in vivo. However, it may have a regulatory role in the immune response.
一氧化氮（NO）已被证明是抵御包括丝虫在内的各种病原体的重要效应机制。Th1细胞因子IFN-γ可诱导NO以及H2O2的产生。因此，已知能引发IFN-γ释放的丝虫线虫微丝蚴（mf）可能是NO释放的靶点。在本研究中，我们发现丝虫物种锡生布鲁线虫的mf对H2O2的攻击具有抗性，但在体外通过化学NO供体以及活化的巨噬细胞暴露于NO时则易受影响。成虫受NO暴露的影响要小得多。在本研究及之前的研究中，注射mf后体内产生的NO表明其在抵御丝虫方面发挥核心作用。然而，无论是药物抑制一氧化氮合成，还是诱导型一氧化氮合酶（iNOS）基因的基因敲除，都没有消除小鼠对循环mf的抗性。然而，有趣的是，与野生型对照相比，iNOS基因敲除小鼠表现出更高的白细胞介素（IL）-2反应和更低的IL-10产生。总之，尽管NO在体外有效，且感染后离体细胞可产生NO，但一氧化氮似乎不是体内消除锡生布鲁线虫mf的重要因素。然而，它可能在免疫反应中具有调节作用。
