Intravenous immunoglobulin preparations attenuate lysolecithin-induced peripheral demyelination in mice and comprise anti-large myelin protein zero antibody

Yuki SETOGUCHI; Akiko HAYASHI; Ayami KAWADA; Ayako IBUSUKI; Daigo YANAOKA; Ryota SAITO; Tomoko ISHIBASHI; Hiroaki TAKIMOTO; Yoshihide YAMAGUCHI; Hirokazu OHTAKI; Hiroko BABA

doi:10.2183/pjab.99.004

Original Article

Intravenous immunoglobulin preparations attenuate lysolecithin-induced peripheral demyelination in mice and comprise anti-large myelin protein zero antibody

Yuki SETOGUCHI, Akiko HAYASHI , Ayami KAWADA, Ayako IBUSUKI, Daigo YANAOKA, Ryota SAITO, Tomoko ISHIBASHI, Hiroaki TAKIMOTO, Yoshihide YAMAGUCHI, Hirokazu OHTAKI, Hiroko BABA

Author information

Yuki SETOGUCHI
https://orcid.org/0000-0003-0778-3100
Department of Functional Neurobiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
Akiko HAYASHI Corresponding author
https://orcid.org/0000-0003-1297-1843
Department of Functional Neurobiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
Ayami KAWADA
https://orcid.org/0000-0001-6580-3355
Department of Functional Neurobiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
Ayako IBUSUKI
https://orcid.org/0000-0002-1929-8762
Department of Functional Neurobiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
Daigo YANAOKA
https://orcid.org/0000-0002-9111-0111
Department of Functional Neurobiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
Ryota SAITO
https://orcid.org/0000-0002-8952-4497
Department of Functional Neurobiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
Tomoko ISHIBASHI
https://orcid.org/0000-0002-8537-0072
Department of Functional Neurobiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
Hiroaki TAKIMOTO
https://orcid.org/0000-0003-0780-7918
Department of Biosciences, School of Science, Kitasato University
Yoshihide YAMAGUCHI
https://orcid.org/0000-0002-5686-9325
Department of Functional Neurobiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
Hirokazu OHTAKI
https://orcid.org/0000-0003-3116-5265
Department of Functional Neurobiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
Hiroko BABA
https://orcid.org/0000-0002-0343-6876
Department of Occupational Therapy, Faculty of Rehabilitation, Niigata University of Health and Welfare

Keywords: intravenous immunoglobulin (IVIg), demyelination, peripheral nerve, neuropathy, lysophosphatidylcholine (lysolecithin), large myelin protein zero (L-MPZ)

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Supplementary material

2023 Volume 99 Issue 2 Pages 48-60

DOI https://doi.org/10.2183/pjab.99.004

Details

Abstract

Intravenous immunoglobulin (IVIg) has been used to treat inflammatory demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain–Barré syndrome, and multifocal motor neuropathy. Despite studies demonstrating the clinical effectiveness of IVIg, the mechanisms underlying its effects remain to be elucidated in detail. Herein, we examined the effects of IVIg on lysolecithin-induced demyelination of the sciatic nerve in a mouse model. Mice —administered with IVIg 1 and 3 days post-injection (dpi) of lysolecithin —exhibited a significantly decreased demyelination area at 7 dpi. Immunoblotting analysis using two different preparations revealed that IVIg reacted with a 36-kDa membrane glycoprotein in the sciatic nerve. Subsequent analyses of peptide absorption identified the protein as a myelin protein in the peripheral nervous system (PNS) known as large myelin protein zero (L-MPZ). Moreover, injected IVIg penetrated the demyelinating lesion, leading to deposition on L-MPZ in the myelin debris. These results indicate that IVIg may modulate PNS demyelination, possibly by binding to L-MPZ on myelin debris.

Corresponding author

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