Tanaka Toshifumi, Furutama Daisuke, Sakai Reiko, Fujita Atsushi, Kimura Fumiharu, Tagami Muneyoshi, Ohsawa Nakaaki, Hanafusa Toshiaki
Aino Institute for Aging Research, Oda 27, Ibaraki-city, Osaka 567-0018, Japan.
Biochim Biophys Acta. 2007 May;1772(5):543-8. doi: 10.1016/j.bbadis.2007.01.011. Epub 2007 Jan 28.
To reveal the biological and pathological roles of anti-GM1 antibody in Guillain-Barré syndrome (GBS), we examined its effects on nerve growth factor (NGF) induced TrkA autophosphorylation (NGF-TrkA signaling) in PC12 cells, a sympathetic nerve cell line. The NGF-TrkA signaling is enhanced by exogenous GM1 ganglioside and this phenomenon is regarded as one of the functional aspects of GM1. The IgGs purified from patients' sera inhibited the NGF-TrkA signaling in GM1 pre-incubated PC12 cells. The degrees of inhibition by IgGs from patients paralleled their immunological reactivity to GM1. In addition, the IgGs also inhibited the neurite outgrowth of NGF-treated PC12 cells. Immunoglobulins in the rabbit sera, which were immunized by GM1, also caused a similar suppressive phenomenon. These results suggested that the anti-GM1 antibody could play roles in pathophysiology in anti-GM1 antibody positive GBS through interfering with the neurotrophic action of NGF and GM1 mediated signal modulation including NGF-TrkA signaling. It is suggested that the modulation of GM1 function is one important action of antibodies and could be one of the important mechanisms in GBS.
为揭示抗GM1抗体在吉兰-巴雷综合征（GBS）中的生物学和病理学作用，我们检测了其对交感神经细胞系PC12细胞中神经生长因子（NGF）诱导的TrkA自磷酸化（NGF-TrkA信号传导）的影响。外源性GM1神经节苷脂可增强NGF-TrkA信号传导，这一现象被视为GM1的功能特性之一。从患者血清中纯化的IgG可抑制预先用GM1孵育的PC12细胞中的NGF-TrkA信号传导。患者来源的IgG的抑制程度与其对GM1的免疫反应性平行。此外，这些IgG还抑制了NGF处理的PC12细胞的神经突生长。用GM1免疫的兔血清中的免疫球蛋白也引起了类似的抑制现象。这些结果表明，抗GM1抗体可能通过干扰NGF的神经营养作用以及GM1介导的包括NGF-TrkA信号传导在内的信号调节，在抗GM1抗体阳性GBS的病理生理学中发挥作用。提示GM1功能的调节是抗体的重要作用之一，可能是GBS的重要发病机制之一。
