Stimulation of monocytes, macrophages, and microglia by amphotericin B and macrophage colony-stimulating factor promotes remyelination.

TitleStimulation of monocytes, macrophages, and microglia by amphotericin B and macrophage colony-stimulating factor promotes remyelination.
Publication TypeJournal Article
Year of Publication2015
AuteursDöring, A, Sloka, S, Lau, L, Mishra, M, van Minnen, J, Zhang, X, Kinniburgh, D, Rivest, S, V Yong, W
JournalJ Neurosci
Volume35
Issue3
Pagination1136-48
Date Published2015 Jan 21
ISSN1529-2401
KeywordsAmphotericin B, Animals, Antifungal Agents, Brain, Demyelinating Diseases, Macrophage Colony-Stimulating Factor, Macrophages, Mice, Microglia, Monocytes, Myelin Sheath, Nerve Regeneration
Abstract

Approaches to stimulate remyelination may lead to recovery from demyelinating injuries and protect axons. One such strategy is the activation of immune cells with clinically used medications, since a properly directed inflammatory response can have healing properties through mechanisms such as the provision of growth factors and the removal of cellular debris. We previously reported that the antifungal medication amphotericin B is an activator of circulating monocytes, and their tissue-infiltrated counterparts and macrophages, and of microglia within the CNS. Here, we describe that amphotericin B activates these cells through engaging MyD88/TRIF signaling. When mice were subjected to lysolecithin-induced demyelination of the spinal cord, systemic injections of nontoxic doses of amphotericin B and another activator, macrophage colony-stimulating factor (MCSF), further elevated the representation of microglia/macrophages at the site of injury. Treatment with amphotericin B, particularly in combination with MCSF, increased the number of oligodendrocyte precursor cells and promoted remyelination within lesions; these pro-regenerative effects were mitigated in mice treated with clodronate liposomes to reduce circulating monocytes and tissue-infiltrated macrophages. Our results have identified candidates among currently used medications as potential therapies for the repair of myelin.

DOI10.1523/JNEUROSCI.1797-14.2015
Alternate JournalJ. Neurosci.
PubMed ID25609628