title: Macrophage colony-stimulating factor aggravates rather than regenerates emphysematous lungs in mice.
abstract: BACKGROUND
  Lung regeneration is an innovative strategy that may cure pulmonary emphysema. The bone marrow (BM) harbors pulmonary stem cells. Hematopoietic cytokine-driven mobilization of BM cells may thus support lung regeneration.
  
  
  OBJECTIVE
  The aim of this study was to determine whether systemic administration of macrophage colony-stimulating factor (M-CSF) leads to the regeneration of lungs in a murine model of elastase-induced emphysema.
  
  
  METHODS
  C57BL/6J mice were administered elastase intratracheally. Four weeks later, in the absence or presence of elastase treatment, mice were intraperitoneally given either M-CSF or saline on days 1-5 each week for 3 weeks. Lung tissue was harvested 24 h after the last injection.
  
  
  RESULTS
  M-CSF administration without prior elastase did not affect the mean linear intercept, surface area, or surface area/lung volume. In contrast, M-CSF administration following elastase injury caused a greater increase in the mean linear intercept and greater decreases in surface area and surface area/lung volume than saline administration following elastase, indicating that M-CSF aggravated emphysema. This aggravation of emphysema was accompanied by accumulation of pulmonary alveolar macrophages (AMs) expressing metalloproteinase (MMP)-9 and MMP-12. M-CSF stimulated AMs to express MMPs in vitro.
  
  
  CONCLUSIONS
  These results suggest that M-CSF administration does not support lung regeneration but rather aggravates the lung destruction associated with elastase injury.
authors.affiliation: First Department of Medicine, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Kazutetsu
authors.initials: K
authors.lastname: Aoshiba
authors.forename: Naoko
authors.initials: N
authors.lastname: Yokohori
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nagai
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004646:Emphysema / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D005557:Formaldehyde; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010196:Pancreatic Elastase / Q000494:pharmacology; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D013552:Swine
chemical_list: D005557:Formaldehyde; D016173:Macrophage Colony-Stimulating Factor; D010196:Pancreatic Elastase