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

A Döring, S Sloka, L Lau, M Mishra… - Journal of …, 2015 - Soc Neuroscience
A Döring, S Sloka, L Lau, M Mishra, J van Minnen, X Zhang, D Kinniburgh, S Rivest…
Journal of Neuroscience, 2015Soc Neuroscience
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 …
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.
Soc Neuroscience