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Fcγ receptor-mediated inflammation inhibits axon regeneration.

Zhang G, Bogdanova N, Gao T, Song JJ, Cragg MS, Glennie MJ, Sheikh KA - PLoS ONE (2014)

Bottom Line: Anti-glycan/ganglioside antibodies are the most common immune effectors found in patients with Guillain-Barré Syndrome, which is a peripheral autoimmune neuropathy.These findings have clinical implications for nerve repair and recovery in antibody-mediated immune neuropathies.Our results add to the complexity of axon regeneration in injured peripheral and central nervous systems as adverse effects of B cells and autoantibodies on neural injury and repair are increasingly recognized.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University of Texas Medical School at Houston, Houston, Texas, United States of America.

ABSTRACT
Anti-glycan/ganglioside antibodies are the most common immune effectors found in patients with Guillain-Barré Syndrome, which is a peripheral autoimmune neuropathy. We previously reported that disease-relevant anti-glycan autoantibodies inhibited axon regeneration, which echo the clinical association of these antibodies and poor recovery in Guillain-Barré Syndrome. However, the specific molecular and cellular elements involved in this antibody-mediated inhibition of axon regeneration are not previously defined. This study examined the role of Fcγ receptors and macrophages in the antibody-mediated inhibition of axon regeneration. A well characterized antibody passive transfer sciatic nerve crush and transplant models were used to study the anti-ganglioside antibody-mediated inhibition of axon regeneration in wild type and various mutant and transgenic mice with altered expression of specific Fcγ receptors and macrophage/microglia populations. Outcome measures included behavior, electrophysiology, morphometry, immunocytochemistry, quantitative real-time PCR, and western blotting. We demonstrate that the presence of autoantibodies, directed against neuronal/axonal cell surface gangliosides, in the injured mammalian peripheral nerves switch the proregenerative inflammatory environment to growth inhibitory milieu by engaging specific activating Fcγ receptors on recruited monocyte-derived macrophages to cause severe inhibition of axon regeneration. Our data demonstrate that the antibody orchestrated Fcγ receptor-mediated switch in inflammation is one mechanism underlying inhibition of axon regeneration. These findings have clinical implications for nerve repair and recovery in antibody-mediated immune neuropathies. Our results add to the complexity of axon regeneration in injured peripheral and central nervous systems as adverse effects of B cells and autoantibodies on neural injury and repair are increasingly recognized.

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Upregulation of Fcγ receptors in nerves of GBS patients.Micrographs showing strong signal of Fcγ common chain in the nerve of a GBS patient but not in a control nerve (A). Western blotting images showing significant upregulation of Fcγ common chain expression in GBS nerves compared to controls (B). Scale bar, 10 µm.
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pone-0088703-g003: Upregulation of Fcγ receptors in nerves of GBS patients.Micrographs showing strong signal of Fcγ common chain in the nerve of a GBS patient but not in a control nerve (A). Western blotting images showing significant upregulation of Fcγ common chain expression in GBS nerves compared to controls (B). Scale bar, 10 µm.

Mentions: Examination of GBS nerves, obtained at different time points after onset, showed that there was significant upregulation of Fcγ common chain in acute (data not shown) and post-acute phase of GBS nerves, whereas control/uninjured human nerves did not show staining for Fcγ common chain (Figure 3A). Western blotting studies confirmed ICC findings (Figure 3B). These results provide evidence that activating FcγRs are upregulated in GBS nerves and injured nerves of experimental animals and are available to participate in Ab-mediated inflammation.


Fcγ receptor-mediated inflammation inhibits axon regeneration.

Zhang G, Bogdanova N, Gao T, Song JJ, Cragg MS, Glennie MJ, Sheikh KA - PLoS ONE (2014)

Upregulation of Fcγ receptors in nerves of GBS patients.Micrographs showing strong signal of Fcγ common chain in the nerve of a GBS patient but not in a control nerve (A). Western blotting images showing significant upregulation of Fcγ common chain expression in GBS nerves compared to controls (B). Scale bar, 10 µm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3921223&req=5

pone-0088703-g003: Upregulation of Fcγ receptors in nerves of GBS patients.Micrographs showing strong signal of Fcγ common chain in the nerve of a GBS patient but not in a control nerve (A). Western blotting images showing significant upregulation of Fcγ common chain expression in GBS nerves compared to controls (B). Scale bar, 10 µm.
Mentions: Examination of GBS nerves, obtained at different time points after onset, showed that there was significant upregulation of Fcγ common chain in acute (data not shown) and post-acute phase of GBS nerves, whereas control/uninjured human nerves did not show staining for Fcγ common chain (Figure 3A). Western blotting studies confirmed ICC findings (Figure 3B). These results provide evidence that activating FcγRs are upregulated in GBS nerves and injured nerves of experimental animals and are available to participate in Ab-mediated inflammation.

Bottom Line: Anti-glycan/ganglioside antibodies are the most common immune effectors found in patients with Guillain-Barré Syndrome, which is a peripheral autoimmune neuropathy.These findings have clinical implications for nerve repair and recovery in antibody-mediated immune neuropathies.Our results add to the complexity of axon regeneration in injured peripheral and central nervous systems as adverse effects of B cells and autoantibodies on neural injury and repair are increasingly recognized.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University of Texas Medical School at Houston, Houston, Texas, United States of America.

ABSTRACT
Anti-glycan/ganglioside antibodies are the most common immune effectors found in patients with Guillain-Barré Syndrome, which is a peripheral autoimmune neuropathy. We previously reported that disease-relevant anti-glycan autoantibodies inhibited axon regeneration, which echo the clinical association of these antibodies and poor recovery in Guillain-Barré Syndrome. However, the specific molecular and cellular elements involved in this antibody-mediated inhibition of axon regeneration are not previously defined. This study examined the role of Fcγ receptors and macrophages in the antibody-mediated inhibition of axon regeneration. A well characterized antibody passive transfer sciatic nerve crush and transplant models were used to study the anti-ganglioside antibody-mediated inhibition of axon regeneration in wild type and various mutant and transgenic mice with altered expression of specific Fcγ receptors and macrophage/microglia populations. Outcome measures included behavior, electrophysiology, morphometry, immunocytochemistry, quantitative real-time PCR, and western blotting. We demonstrate that the presence of autoantibodies, directed against neuronal/axonal cell surface gangliosides, in the injured mammalian peripheral nerves switch the proregenerative inflammatory environment to growth inhibitory milieu by engaging specific activating Fcγ receptors on recruited monocyte-derived macrophages to cause severe inhibition of axon regeneration. Our data demonstrate that the antibody orchestrated Fcγ receptor-mediated switch in inflammation is one mechanism underlying inhibition of axon regeneration. These findings have clinical implications for nerve repair and recovery in antibody-mediated immune neuropathies. Our results add to the complexity of axon regeneration in injured peripheral and central nervous systems as adverse effects of B cells and autoantibodies on neural injury and repair are increasingly recognized.

Show MeSH
Related in: MedlinePlus