Macrophage colony-stimulating factor aggravates rather than regenerates emphysematous lungs in mice.
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.
Ishikawa
Takaaki
T
First Department of Medicine, Tokyo Women's Medical University, Tokyo, Japan.
Aoshiba
Kazutetsu
K
Yokohori
Naoko
N
Nagai
Atsushi
A
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
D005557:Formaldehyde; D016173:Macrophage Colony-Stimulating Factor; D010196:Pancreatic Elastase