title: Skeletal muscle is enriched in hematopoietic stem cells and not inflammatory cells in cachectic mice.
abstract: OBJECTIVE
  Cachexia, a debilitating syndrome characterized by skeletal muscle wasting, is associated to many chronic diseases and diminishes the quality of life and survival of patients. Tumor-derived factors and proinflammatory cytokines, including TNF-alpha, IL-6 and IL-1 beta, mediate cachexia. In response to elevated cytokine levels, increased proteasome-mediated proteolysis and auto-phagocytosis result in muscle wasting. The histologic features of muscle cachexia are not fully elucidated. Therefore, we analysed alterations of different cell populations in cachectic muscle.
  
  
  METHODS
  By immunohistochemical and cytological approaches, we characterized changes in the abundance of cellular populations in the musculature of a murine model of cancer cachexia (C26-bearing mice).
  
  
  RESULTS
  Cachectic muscle displayed a decreased DNA content proportional to muscle mass wastage. A decrease in the number of nuclei occurred in the muscular but not in the stromal compartment. Cachectic muscle showed: mild modulation of myeloperoxidase activity, a neutrophil marker; reduction of macrophages in the endomysium; decrease in CD3(+) lymphocyte number. Conversely, a statistically significant enrichment in Sca-1(+) CD45(+) hematopoietic stem cells (HSCs) occurred in cachectic muscle.
  
  
  CONCLUSIONS
  The elevated levels of cytokines which characterize cachexia may represent a trigger for inflammatory cell activation. However, we find that in cachexia, inflammatory cells in muscle are not increased while muscle tissue nuclei decline. Our data suggest that the inflammatory cell-mediated stress is not an etiologic component of muscle wasting in cachexia. The relative increase in HSCs in cachectic skeletal muscle suggests an attempt to maintain muscle homeostasis by recruitment and/or activation of stem cells.
authors.affiliation: Department of Histology and Medical Embryology, Sapienza University of Rome, Interuniversity Institute of Myology, Via Scarpa, 14 00161 Rome, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Berardi
authors.forename: Paola
authors.initials: P
authors.lastname: Aulino
authors.forename: Ivana
authors.initials: I
authors.lastname: Murfuni
authors.forename: Angelica
authors.initials: A
authors.lastname: Toschi
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Padula
authors.forename: Bianca M
authors.initials: BM
authors.lastname: Scicchitano
authors.forename: Dario
authors.initials: D
authors.lastname: Coletti
authors.forename: Sergio
authors.initials: S
authors.lastname: Adamo
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D001835:Body Weight; D002100:Cachexia / Q000150:complications / Q000209:etiology / Q000473:pathology*; D004247:DNA / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008214:Lymphocytes / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000473:pathology*; D009133:Muscular Atrophy / Q000209:etiology; D009250:NADP Transhydrogenases / Q000378:metabolism; D009369:Neoplasms / Q000150:complications; D009195:Peroxidase / Q000378:metabolism; D013997:Time Factors
chemical_list: D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D004247:DNA; D009195:Peroxidase; D009250:NADP Transhydrogenases; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse