title: Inflammatory cells and apoptosis in respiratory and limb muscles of patients with COPD.
abstract: Discrepancies exist regarding the involvement of cellular inflammation and apoptosis in the muscle dysfunction of chronic obstructive pulmonary disease (COPD) patients with preserved body composition. We explored whether levels of inflammatory cells and apoptosis were increased in both respiratory and limb muscles of COPD patients without nutritional abnormalities. In the vastus lateralis, external intercostals, and diaphragms of severe and moderate COPD patients with normal body composition, and in healthy subjects, intramuscular leukocytes and macrophage levels were determined (immunohistochemistry). Muscle structure was also evaluated. In the diaphragm and vastus lateralis of severe and moderate COPD patients and controls, apoptotic nuclei were explored using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, electron microscopy, and caspase-3 expression. In COPD patients compared with controls, diaphragm and intercostal levels of inflammatory cells were extremely low and not significantly different. However, in the vastus lateralis of the severe patients, inflammatory cell counts, although also very low, were significantly greater. In those patients, TUNEL-positive nuclei levels were also significantly greater in diaphragms and vastus lateralis. A significant inverse relationship was found between quadriceps TUNEL-positive nuclei levels and muscle force. Ultrastructural apoptotic nuclei revealed no differences in respiratory or limb muscles between COPD patients and controls. Muscle caspase-3 expression did not differ between patients and controls. In severe COPD patients with preserved body composition, while increased apoptotic nuclei seems to be a contributor to their muscle dysfunction, cellular inflammation does not. The increased numbers of TUNEL-positive nuclei in their muscles suggest that they may also be exposed to a continuous repair/remodeling process.
authors.affiliation: Pulmonology Dept. and Muscle and Respiratory System Research Unit, IMIM-Hospital del Mar, PRBB, Dr. Aiguader, 88, E-08003 Barcelona, Spain. ebarreiro@imim.es
authors.forename: Esther
authors.initials: E
authors.lastname: Barreiro
authors.forename: Dolores
authors.initials: D
authors.lastname: Ferrer
authors.forename: Francisco
authors.initials: F
authors.lastname: Sanchez
authors.forename: Joan
authors.initials: J
authors.lastname: Minguella
authors.forename: Judith
authors.initials: J
authors.lastname: Marin-Corral
authors.forename: Juana
authors.initials: J
authors.lastname: Martinez-Llorens
authors.forename: Josep
authors.initials: J
authors.lastname: Lloreta
authors.forename: Joaquim
authors.initials: J
authors.lastname: Gea
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D017209:Apoptosis; D001706:Biopsy; D016022:Case-Control Studies; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007962:Leukocytes / Q000276:immunology; D035002:Lower Extremity; D008264:Macrophages / Q000276:immunology; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D053580:Muscle Strength; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D052097:Quadriceps Muscle / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D012132:Respiratory Muscles / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D012720:Severity of Illness Index