, 2011).The injection of BMDMC even in normal lungs led to neutrophil increase in lung tissue, with no functional effects. This increment may be attributed to: presence of neutrophils in the pool of BMDMC and/or recruitment of these Protein Tyrosine Kinase inhibitor cells by chemoattractive stimuli (Araújo et al., 2010, Prota et al., 2010, Abreu et al., 2011a and Maron-Gutierrez

et al., 2011). Several studies have reported that circulating precursor cells are reduced (Bonsignore et al., 2006 and Huertas et al., 2010), and that VEGF-dependent precursor cell mobilization is impaired (Hattori et al., 2001) in human COPD. In this line, the administration of exogenous BMDMC in the current study might have contributed to the reduction of airway epithelial cell damage, tissue remodeling and inflammatory processes by increasing the available pool of circulating precursor cells. We demonstrated that early BMDMC administration led to less hyperinflation and collapsed areas as well as inflammatory cell infiltration

in the lung parenchyma, reduced small airways collagen deposition, and elastic fiber preservation. This is in agreement with a recent report that mechanical force-induced failure of the locally weakened collagen is correlated to structural changes in the lung undergoing heterogeneous consequences of elastase injury (Hamakawa et al., 2010). Ultrastructural analysis selleck inhibitor using electron microscopy revealed higher preservation of endothelial cells, type II pneumocyte and basement membrane, associated with reduction of collagen fiber deposition and elastic fiber breakdown. Besides, several typical features of regenerative processes, such as enlarged type II pneumocytes with augmented lamellar bodies, as well as the presence of multinucleated and undifferentiated cells in lung parenchyma were observed in the E-CELL group, suggesting that BMDMC may modulate elastase injury and play an important role in the repair of damaged areas. However, the exact mechanisms responsible for cell restoration remain unclear. It has been suggested that these multinucleated

Montelukast Sodium cells could be the result of a fusion between macrophages and BMDMCs, or between macrophages and injured epithelial cells (Krause, 2008). Additionally, it has been described that macrophages behave in vitro as stem cell attractors. Once at the site of injury, the ability of precursor cells to reconstitute the damaged tissues depends on the signals generated in situ by the macrophages ( Lolmede et al., 2009). Besides their proven plasticity, most beneficial effects of stem cells have been attributed to paracrine effects, that is, a capacity of modulating cytokines and growth factor synthesis without being present at the injury site (Abreu et al., 2011b and Doorn et al., 2011). Paracrine effects have been demonstrated in several models of lung diseases, including emphysema (Shigemura et al., 2006, Zhen et al., 2010, Huh et al.