Abstract
Tissue repair often occurs in organs damaged by an inflammatory response. Inflammatory stimuli induce a rapid and massive release of inflammatory cells including neutrophils from the bone marrow. Many recent studies have suggested that bone marrow cells have the potential to differentiate into a variety of cell types. However, whether inflammatory stimuli induce a release of bone marrow-derived progenitor cells (BMPCs) , or how much impact the suppression of BMPCs has on the injured organ is not clear. Here, we show that lipopolysaccharide (LPS) induces a rapid mobilization of BMPC into the circulation. BMPC accumulate within the inflammatory site and differentiate to become capillary endothelial and alveolar epithelial cells. Moreover, the suppression of BMPCs prior to intra-pulmonary LPS leads to the disruption of tissue structure and emphysema-like changes. Then, the role of BMPCs on lung regeneration was evaluated using a murine emphysema model. Treatment with either all-trans-retinoic-acid, known to activate genes involved in lung development and promote alveolar septation and lung growth, or granulocyte-colony stimulating factor, known as the factor mobilizing hematopoietic and mesenchymal lineage cells from bone marrow, promotes lung regeneration and an increase in BMPCs in alveoli. These data suggest that BMPCs are important and required for lung repair and regeneration.
