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. OBJECTIVES: 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.
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. OBJECTIVES: 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: Pınar Yıldız Gülhan; Mehmet Savaş Ekici; Mehmet Niyaz; Muhammet Gülhan; Mustafa Emre Erçin; Aydanur Ekici; Nurkan Aksoy Journal: Turk Thorac J Date: 2020-01-01
Authors: S Pourteymour; K Eckardt; T Holen; T Langleite; Sindre Lee; J Jensen; K I Birkeland; C A Drevon; M Hjorth Journal: Mol Metab Date: 2017-01-29 Impact factor: 7.422
Authors: Mai Tsutsui; Chung Yan Cheung; Takeyuki Wada; Jen-Erh Jaw; Cheng Wei Tony Yang; Pascal Bernatchez; Zoe White; Chen Xi Yang; Eun Jeong Annie Bae; Lauren H Choi; Dan Gelbart; Samuel Lichtenstein; Lindsay Machan; Eran Elizur; Kim Wolff; Evan Goodacre; Marek Lipnicki; Denny Wong; Don D Sin Journal: Sci Rep Date: 2021-10-08 Impact factor: 4.379
Authors: Lars Lüthje; Tobias Raupach; Hellmuth Michels; Bernhard Unsöld; Gerd Hasenfuss; Harald Kögler; Stefan Andreas Journal: Respir Res Date: 2009-01-28