Biological roles of anti-GM1 antibodies in patients with Guillain-Barré syndrome for nerve growth factor signaling.
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.
Tanaka
Toshifumi
T
Aino Institute for Aging Research, Oda 27, Ibaraki-city, Osaka 567-0018, Japan.
Furutama
Daisuke
D
Sakai
Reiko
R
Fujita
Atsushi
A
Kimura
Fumiharu
F
Tagami
Muneyoshi
M
Ohsawa
Nakaaki
N
Hanafusa
Toshiaki
T
D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000502:physiology*; D005260:Female; D005677:G(M1) Ganglioside / Q000276:immunology*; D020275:Guillain-Barre Syndrome / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000502:physiology*; D016716:PC12 Cells; D010766:Phosphorylation; D051381:Rats; D020917:Receptor, trkA / Q000378:metabolism*; D015398:Signal Transduction
D001323:Autoantibodies; D005677:G(M1) Ganglioside; D020932:Nerve Growth Factor; D020917:Receptor, trkA