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Open Access 01-12-2015 | Research

Immunoglobulins stimulate cultured Schwann cell maturation and promote their potential to induce axonal outgrowth

Authors: Nevena Tzekova, André Heinen, Sebastian Bunk, Corinna Hermann, Hans-Peter Hartung, Birgit Reipert, Patrick Küry

Published in: Journal of Neuroinflammation | Issue 1/2015

Abstract

Background

Schwann cells are the myelinating glial cells of the peripheral nervous system and exert important regenerative functions revealing them as central repair components of many peripheral nerve pathologies. Intravenous immunoglobulins (IVIG) are widely used to treat autoimmune and inflammatory diseases including immune-mediated neuropathies. Nevertheless, promotion of peripheral nerve regeneration is currently an unmet therapeutical goal. We therefore examined whether immunoglobulins affect glial cell homeostasis, differentiation, and Schwann cell dependent nerve regenerative processes.

Methods

The responses of different primary Schwann cell culture models to IVIG were investigated: immature or differentiation competent Schwann cells, myelinating neuron/glial cocultures, and dorsal root ganglion explants. Immature or differentiating Schwann cells were used to study cellular proliferation, morphology, and gene/protein expression. Myelination rates were determined using myelinating neuron/glia cocultures, whereas axonal outgrowth was assessed using non-myelinating dorsal root ganglion explants.

Results

We found that IVIG specifically bind to Schwann cells and detected CD64 Fc receptor expression on their surface. In response to IVIG binding, Schwann cells reduced proliferation rates and accelerated growth of cellular protrusions. Furthermore, we observed that IVIG treatment transiently boosts myelin gene expression and myelination-related signaling pathways of immature cells, whereas in differentiating Schwann cells, myelin expression is enhanced on a long-term scale. Importantly, myelin gene upregulation was not detected upon application of IgG1 control antibodies. In addition, we demonstrate for the first time that Schwann cells secrete interleukin-18 upon IVIG stimulation and that this cytokine instructs these cells to promote axonal growth.

Conclusions

We conclude that IVIG can positively influence the Schwann cell differentiation process and that it enhances their regenerative potential.

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Title: Immunoglobulins stimulate cultured Schwann cell maturation and promote their potential to induce axonal outgrowth
Authors: Nevena Tzekova
André Heinen
Sebastian Bunk
Corinna Hermann
Hans-Peter Hartung
Birgit Reipert
Patrick Küry
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2015
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-015-0331-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Immunoglobulins stimulate cultured Schwann cell maturation and promote their potential to induce axonal outgrowth

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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