RT Journal Article
SR Electronic
T1 Resistive breathing induces matrix metalloproteinases-9 and -12 expression in the lung
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P4638
VO 40
IS Suppl 56
A1 Dimitrios Toumpanakis
A1 Olga Noussia
A1 Ioanna Sigala
A1 Tatianna Michailidou
A1 Vasso Karavana
A1 Charalampos Roussos
A1 Stamatios Theocharis
A1 Theodoros Vassilakopoulos
YR 2012
UL http://erj.ersjournals.com/content/40/Suppl_56/P4638.abstract
AB Resistive breathing (RB), encountered in obstructive airway diseases, is associated with large negative intrathoracic pressures and has been recently shown to induce acute lung injury and inflammation. Matrix metalloproteinases (MMP)-9 and -12, implicated in the pathogenesis of both asthma and COPD, are upregulated by inflammation and by mechanical stress per se. We hypothesized that RB induces MMP9 and -12 expression and activity in the lung.Anesthetized, tracheostomised rats were breathing through a 2-way valve. The inspiratory line was connected to a resistance setting peak tracheal pressure at 50% of maximum (RB). Quietly breathing animals served as controls. After 3 and 6hrs of RB, bronchoalveolar lavage (BAL) was performed to measure cell count and cytokine levels by ELISA. Lung injury was evaluated by histology. MMP9 lung levels were measured by zymography and immunohistochemistry (IHC). MMP12 was detected by IHC. Alveolar macrophages from normal rats were incubated with BAL fluid from rats that underwent RB. MMP9 activity was measured in cell supernatants by zymography.After 3 and 6hrs of RB, lung injury was detected by histology. Increased numbers of alveolar macrophages and neutrophils (p<0.05) and increased levels of IL1b and IL6 (p<0.01) were measured in the BAL following 6hrs of RB. MMP9 activity raised by 2-fold after 6hrs of RB (p<0.001). MMP9 was detected in alveolar macrophages and epithelial cells. After 3 and 6hrs of RB, increased levels of MMP12 were detected in alveolar macrophages. BAL fluid from animals that underwent 6hrs of RB, induced MMP9 in supernatants by 7.5-fold (p<0.001).In previously healthy rats, RB resulted in increased MMP9 and -12 expression in the lung.