Bingisser R M, Tilbrook P A, Holt P G, Kees U R
TVW Telethon Institute for Child Health Research, Division of Cell Biology, West Perth, Australia.
J Immunol. 1998 Jun 15;160(12):5729-34.
Nitric oxide (NO) has been invoked as an important pathogenic factor in a wide range of immunologically mediated diseases. The present study demonstrates that macrophage-derived NO may conversely function to fine tune T cell-mediated inflammation via reversible dephosphorylation of intracellular signaling molecules, which are involved in the control of T cell proliferation. Thus, T cells activated in the presence of alveolar macrophages are unable to proliferate despite expression of IL-2R and secretion of IL-2. This process is reproduced by the NO generator S-nitroso-N-acetylpenicillamine and is inhibitable by the NO synthase inhibitor N(G)-methyl-L-arginine. Analysis of T cell lysates by immunoprecipitation with specific Abs and subsequent immunoblotting indicated marked reduction of tyrosine phosphorylation of Jak3 and STAT5 mediated by NO. Further studies indicated that NO-mediated T cell suppression was reversible by the guanylate cyclase inhibitors methylene blue and LY-83583 and was reproduced by a cell-permeable analogue of cyclic GMP, implicating guanylate cyclase activation as a key step in the inhibition of T cell activation by NO.
一氧化氮（NO）被认为是多种免疫介导疾病中的重要致病因素。本研究表明，巨噬细胞衍生的NO可能通过参与控制T细胞增殖的细胞内信号分子的可逆去磷酸化，反过来发挥微调T细胞介导炎症的作用。因此，尽管存在白细胞介素-2受体（IL-2R）表达和白细胞介素-2（IL-2）分泌，但在肺泡巨噬细胞存在下激活的T细胞无法增殖。此过程可由NO生成剂S-亚硝基-N-乙酰青霉胺重现，并可被NO合酶抑制剂N（G）-甲基-L-精氨酸抑制。用特异性抗体进行免疫沉淀并随后进行免疫印迹分析T细胞裂解物，结果表明NO介导的Jak3和STAT5酪氨酸磷酸化显著减少。进一步研究表明，鸟苷酸环化酶抑制剂亚甲蓝和LY-83583可使NO介导的T细胞抑制作用逆转，且细胞可渗透的环磷酸鸟苷（cGMP）类似物可重现该作用，这表明鸟苷酸环化酶激活是NO抑制T细胞活化的关键步骤。
