Induction of paranodal myelin detachment and sodium channel loss in vivo by Campylobacter jejuni DNA-binding protein from starved cells (C-Dps) in myelinated nerve fibers

Hua Piao, Motozumi Minohara, Nobutoshi Kawamura, Wei Li, Yoshimitsu Mizunoe, Fujio Umehara, Yoshinobu Goto, Susumu Kusunoki, Takuya Matsushita, Kazuhiro Ikenaka, Takashi Maejima, Jun ichi Nabekura, Ryo Yamasaki, Jun-Ichi Kira

研究成果: ジャーナルへの寄稿記事

7 引用 (Scopus)

抄録

In an axonal variant of Guillain-Barré syndrome (GBS) associated with Campylobacter jejuni (C. jejuni) enteritis, the mechanism underlying axonal damage is obscure. We purified and characterized a DNA-binding protein from starved cells derived from C. jejuni (C-Dps). This C-Dps protein has significant homology with Helicobacter pylori neutrophil-activating protein (HP-NAP), which is chemotactic for human neutrophils through binding to sulfatide. Because sulfatide is essential for paranodal junction formation and for the maintenance of ion channels on myelinated axons, we examined the in vivo effects of C-Dps. First, we found that C-Dps specifically binds to sulfatide by ELISA and immunostaining of thin-layer chromatograms loaded with various glycolipids. Double immunostaining of peripheral nerves exposed to C-Dps with anti-sulfatide antibody and anti-C-Dps antibody revealed co-localization of them. When C-Dps was injected into rat sciatic nerves, it densely bound to the outermost parts of the myelin sheath and nodes of Ranvier. Injection of C-Dps rapidly induced paranodal myelin detachment and axonal degeneration; this was not seen following injection of PBS or heat-denatured C-Dps. Electron microscopically, C-Dps-injected nerves showed vesiculation of the myelin sheath at the nodes of Ranvier. Nerve conduction studies disclosed a significant reduction in compound muscle action potential amplitudes in C-Dps-injected nerves compared with pre-injection values, but not in PBS-, heat-denatured C-Dps-, or BSA-injected nerves. However, C-Dps did not directly affect Na+ currents in dissociated hippocampal neurons. Finally, when C-Dps was intrathecally infused into rats, it was deposited in a scattered pattern in the cauda equina, especially in the outer part of the myelin sheath and the nodal region. In C-Dps-infused rats, but not in BSA-infused ones, a decrease in the number of sodium channels, vesiculation of the myelin sheath, axonal degeneration and infiltration of Iba-1-positive macrophages were observed. Thus, we consider that C-Dps damages myelinated nerve fibers, possibly through interference with paranodal sulfatide function, and may contribute to the axonal pathology seen in C. jejuni-related GBS.

元の言語英語
ページ(範囲)54-62
ページ数9
ジャーナルJournal of the Neurological Sciences
288
発行部数1-2
DOI
出版物ステータス出版済み - 1 15 2010

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Sulfoglycosphingolipids
Myelinated Nerve Fibers
Campylobacter jejuni
Sodium Channels
DNA-Binding Proteins
Myelin Sheath
Ranvier's Nodes
Injections
Hot Temperature
Cauda Equina
Enteritis
Glycolipids
Neural Conduction
Sciatic Nerve
Protein C
Ion Channels
Peripheral Nerves
Action Potentials
Axons
Anti-Idiotypic Antibodies

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

これを引用

Induction of paranodal myelin detachment and sodium channel loss in vivo by Campylobacter jejuni DNA-binding protein from starved cells (C-Dps) in myelinated nerve fibers. / Piao, Hua; Minohara, Motozumi; Kawamura, Nobutoshi; Li, Wei; Mizunoe, Yoshimitsu; Umehara, Fujio; Goto, Yoshinobu; Kusunoki, Susumu; Matsushita, Takuya; Ikenaka, Kazuhiro; Maejima, Takashi; Nabekura, Jun ichi; Yamasaki, Ryo; Kira, Jun-Ichi.

:: Journal of the Neurological Sciences, 巻 288, 番号 1-2, 15.01.2010, p. 54-62.

研究成果: ジャーナルへの寄稿記事

Piao, Hua ; Minohara, Motozumi ; Kawamura, Nobutoshi ; Li, Wei ; Mizunoe, Yoshimitsu ; Umehara, Fujio ; Goto, Yoshinobu ; Kusunoki, Susumu ; Matsushita, Takuya ; Ikenaka, Kazuhiro ; Maejima, Takashi ; Nabekura, Jun ichi ; Yamasaki, Ryo ; Kira, Jun-Ichi. / Induction of paranodal myelin detachment and sodium channel loss in vivo by Campylobacter jejuni DNA-binding protein from starved cells (C-Dps) in myelinated nerve fibers. :: Journal of the Neurological Sciences. 2010 ; 巻 288, 番号 1-2. pp. 54-62.
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abstract = "In an axonal variant of Guillain-Barr{\'e} syndrome (GBS) associated with Campylobacter jejuni (C. jejuni) enteritis, the mechanism underlying axonal damage is obscure. We purified and characterized a DNA-binding protein from starved cells derived from C. jejuni (C-Dps). This C-Dps protein has significant homology with Helicobacter pylori neutrophil-activating protein (HP-NAP), which is chemotactic for human neutrophils through binding to sulfatide. Because sulfatide is essential for paranodal junction formation and for the maintenance of ion channels on myelinated axons, we examined the in vivo effects of C-Dps. First, we found that C-Dps specifically binds to sulfatide by ELISA and immunostaining of thin-layer chromatograms loaded with various glycolipids. Double immunostaining of peripheral nerves exposed to C-Dps with anti-sulfatide antibody and anti-C-Dps antibody revealed co-localization of them. When C-Dps was injected into rat sciatic nerves, it densely bound to the outermost parts of the myelin sheath and nodes of Ranvier. Injection of C-Dps rapidly induced paranodal myelin detachment and axonal degeneration; this was not seen following injection of PBS or heat-denatured C-Dps. Electron microscopically, C-Dps-injected nerves showed vesiculation of the myelin sheath at the nodes of Ranvier. Nerve conduction studies disclosed a significant reduction in compound muscle action potential amplitudes in C-Dps-injected nerves compared with pre-injection values, but not in PBS-, heat-denatured C-Dps-, or BSA-injected nerves. However, C-Dps did not directly affect Na+ currents in dissociated hippocampal neurons. Finally, when C-Dps was intrathecally infused into rats, it was deposited in a scattered pattern in the cauda equina, especially in the outer part of the myelin sheath and the nodal region. In C-Dps-infused rats, but not in BSA-infused ones, a decrease in the number of sodium channels, vesiculation of the myelin sheath, axonal degeneration and infiltration of Iba-1-positive macrophages were observed. Thus, we consider that C-Dps damages myelinated nerve fibers, possibly through interference with paranodal sulfatide function, and may contribute to the axonal pathology seen in C. jejuni-related GBS.",
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T1 - Induction of paranodal myelin detachment and sodium channel loss in vivo by Campylobacter jejuni DNA-binding protein from starved cells (C-Dps) in myelinated nerve fibers

AU - Piao, Hua

AU - Minohara, Motozumi

AU - Kawamura, Nobutoshi

AU - Li, Wei

AU - Mizunoe, Yoshimitsu

AU - Umehara, Fujio

AU - Goto, Yoshinobu

AU - Kusunoki, Susumu

AU - Matsushita, Takuya

AU - Ikenaka, Kazuhiro

AU - Maejima, Takashi

AU - Nabekura, Jun ichi

AU - Yamasaki, Ryo

AU - Kira, Jun-Ichi

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N2 - In an axonal variant of Guillain-Barré syndrome (GBS) associated with Campylobacter jejuni (C. jejuni) enteritis, the mechanism underlying axonal damage is obscure. We purified and characterized a DNA-binding protein from starved cells derived from C. jejuni (C-Dps). This C-Dps protein has significant homology with Helicobacter pylori neutrophil-activating protein (HP-NAP), which is chemotactic for human neutrophils through binding to sulfatide. Because sulfatide is essential for paranodal junction formation and for the maintenance of ion channels on myelinated axons, we examined the in vivo effects of C-Dps. First, we found that C-Dps specifically binds to sulfatide by ELISA and immunostaining of thin-layer chromatograms loaded with various glycolipids. Double immunostaining of peripheral nerves exposed to C-Dps with anti-sulfatide antibody and anti-C-Dps antibody revealed co-localization of them. When C-Dps was injected into rat sciatic nerves, it densely bound to the outermost parts of the myelin sheath and nodes of Ranvier. Injection of C-Dps rapidly induced paranodal myelin detachment and axonal degeneration; this was not seen following injection of PBS or heat-denatured C-Dps. Electron microscopically, C-Dps-injected nerves showed vesiculation of the myelin sheath at the nodes of Ranvier. Nerve conduction studies disclosed a significant reduction in compound muscle action potential amplitudes in C-Dps-injected nerves compared with pre-injection values, but not in PBS-, heat-denatured C-Dps-, or BSA-injected nerves. However, C-Dps did not directly affect Na+ currents in dissociated hippocampal neurons. Finally, when C-Dps was intrathecally infused into rats, it was deposited in a scattered pattern in the cauda equina, especially in the outer part of the myelin sheath and the nodal region. In C-Dps-infused rats, but not in BSA-infused ones, a decrease in the number of sodium channels, vesiculation of the myelin sheath, axonal degeneration and infiltration of Iba-1-positive macrophages were observed. Thus, we consider that C-Dps damages myelinated nerve fibers, possibly through interference with paranodal sulfatide function, and may contribute to the axonal pathology seen in C. jejuni-related GBS.

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