RESUMEN
Impaired recovery of aged muscle following a disuse event is an unresolved issue facing the older adult population. Although investigations in young animals have suggested that rapid regrowth of skeletal muscle following a disuse event entails a coordinated involvement of skeletal muscle macrophages, this phenomenon has not yet been thoroughly tested as an explanation for impaired muscle recovery in aging. To examine this hypothesis, young (4-5 mo) and old (24-26 mo) male mice were examined as controls following 2 wk of hindlimb unloading (HU) and following 4 (RL4) and 7 (RL7) days of reloading after HU. Muscles were harvested to assess muscle weight, myofiber-specifc cross-sectional area, and skeletal muscle macrophages via immunofluorescence. Flow cytometry was used on gastrocnemius and soleus muscle (at RL4) single-cell suspensions to immunophenotype skeletal muscle macrophages. Our data demonstrated impaired muscle regrowth in aged compared with young mice following disuse, which was characterized by divergent muscle macrophage polarization patterns and muscle-specifc macrophage abundance. During reloading, young mice exhibited the classical increase in M1-like (MHC II+CD206-) macrophages that preceeded the increase in percentage of M2-like macrophages (MHC II-CD206+); however, old mice did not demonstrate this pattern. Also, at RL4, the soleus demonstrated reduced macrophage abundance with aging. Together, these data suggest that dysregulated macrophage phenotype patterns in aged muscle during recovery from disuse may be related to impaired muscle growth. Further investigation is needed to determine whether the dysregulated macrophage response in the old during regrowth from disuse is related to a reduced ability to recruit or activate specific immune cells.
Asunto(s)
Envejecimiento/fisiología , Polaridad Celular/fisiología , Suspensión Trasera/fisiología , Macrófagos/fisiología , Músculo Esquelético/patología , Atrofia Muscular/rehabilitación , Animales , Activación de Macrófagos/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Músculo Esquelético/citología , Músculo Esquelético/inmunología , Atrofia Muscular/patología , Condicionamiento Físico Animal/fisiologíaRESUMEN
BACKGROUND: Eosinophilic granulomatosis with polyangiitis is a rare, necrotizing systemic vasculitis associated with asthma and hypereosinophilia. Its cause and pathophysiology are still being elucidated. CASE PRESENTATION: We report a case of eosinophilic granulomatosis with polyangiitis in a 50-year-old Caucasian woman who presented with chest pain, dyspnea at rest, fever, and periorbital swelling. She was found to have significant hypereosinophilia and cardiac tamponade physiology. A biopsy confirmed extensive infiltration of both lungs and pericardium by eosinophils. She did not have any anti-neutrophil cytoplasmic antibodies. CONCLUSIONS: Eosinophilic granulomatosis with polyangiitis diagnosis does not require the presence of anti-neutrophil cytoplasmic antibodies. Anti-neutrophil cytoplasmic antibody-positive and anti-neutrophil cytoplasmic antibody-negative eosinophilic granulomatosis with polyangiitis may present with different clinical phenotypes, perhaps suggesting two distinct disease etiologies and distinct pathophysiology.
Asunto(s)
Taponamiento Cardíaco/etiología , Síndrome de Churg-Strauss/complicaciones , Edema/etiología , Eosinofilia/complicaciones , Pulmón/patología , Órbita , Pericardio/patología , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Biopsia , Síndrome de Churg-Strauss/inmunología , Disnea/etiología , Eosinofilia/patología , Femenino , Fiebre/etiología , Humanos , Persona de Mediana EdadRESUMEN
Skeletal muscle is essential for mobility, stability and whole body metabolism, and muscle loss, for instance, during sarcopenia, has profound consequences. Satellite cells (muscle stem cells) have been hypothesized, but not yet demonstrated, to contribute to muscle homeostasis and a decline in their contribution to myofibre homeostasis to play a part in sarcopenia. To test their role in muscle maintenance, we genetically labelled and ablated satellite cells in adult sedentary mice. We demonstrate via genetic lineage experiments that, even in the absence of injury, satellite cells contribute to myofibres in all adult muscles, although the extent and timing differs. However, genetic ablation experiments showed that satellite cells are not globally required to maintain myofibre cross-sectional area of uninjured adult muscle.
Asunto(s)
Fibras Musculares Esqueléticas/patología , Alelos , Animales , Cruzamientos Genéticos , Proteínas Fluorescentes Verdes/metabolismo , Homeostasis , Masculino , Ratones , Ratones Endogámicos C57BL , Factor de Transcripción PAX7/metabolismo , Regeneración , Sarcopenia/genética , Células Satélite del Músculo Esquelético/citología , Factores de TiempoRESUMEN
Adult muscle's exceptional capacity for regeneration is mediated by muscle stem cells, termed satellite cells. As with many stem cells, Wnt/ß-catenin signaling has been proposed to be critical in satellite cells during regeneration. Using new genetic reagents, we explicitly test in vivo whether Wnt/ß-catenin signaling is necessary and sufficient within satellite cells and their derivatives for regeneration. We find that signaling is transiently active in transit-amplifying myoblasts, but is not required for regeneration or satellite cell self-renewal. Instead, downregulation of transiently activated ß-catenin is important to limit the regenerative response, as continuous regeneration is deleterious. Wnt/ß-catenin activation in adult satellite cells may simply be a vestige of their developmental lineage, in which ß-catenin signaling is critical for fetal myogenesis. In the adult, surprisingly, we show that it is not activation but rather silencing of Wnt/ß-catenin signaling that is important for muscle regeneration.