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Title: Determining the role Of CD68 positive macrophages in muscle damage and disease
Author: Roberts, H.
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2020
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Macrophages play an essential role in the immune response, responding to pathogens, inflammation and tissue damage. Proinflammatory macrophages are prevalent in the X- linked life limiting muscle wasting disease, Duchenne Muscular Dystrophy (DMD), where they are thought to exacerbate muscle damage. We hypothesise that reducing numbers of a specific subset of macrophages may reduce the muscle damage seen in DMD without effecting regeneration of the muscle. The MacLow mouse model allows the doxycycline inducible depletion of CD68 positive (CD68+) macrophages. We crossed the mdx mouse model of DMD with the MacLow model to generate the mdxMacLow model (MacLowMD). This study aimed to determine the effects of macrophage depletion on muscle damage and regeneration in muscular dystrophy using the MacLowMD model. Doxycycline treated MacLowMD mice had a 33% reduction in total macrophage population in the liver (P<0.05). No difference was found in the number of CD68+ cells in Tibialis Anterior (TA) and quadricep muscle of doxycycline treated MacLowMD mice compared to mdx mice, but a 30% reduction (P<0.05) was observed in diaphragm and heart muscle. A significant increase in numbers of M2, CD206 positive (CD206+) and CD163 positive (CD163+) macrophages was observed throughout all muscles studied (P<0.05). A significant (P<0.05) reduction in muscle fibre damage was observed between doxycycline treated MacLowMD muscle compared to mdx muscle, and doxycycline treatment and CD68+ macrophage depletion had no negative effects on the regenerative capacity in any of the muscles studied. These results demonstrate that the MacLowMD model is a good model for studying the role of proinflammatory CD68+ macrophages in disease progression, muscle damage and muscle regeneration.
Supervisor: Miller, G. ; Garland, A. ; Chapman, N. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available