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Mechanical ventilation (MV) could prime the lung toward an inflammatory response if exposed to another insult such as bacterial invasion. The underlying mechanisms are not so far clear. Toll-like receptors (TLRs) allow the host to recognize selectively bacterial pathogens and in turn to trigger an immune response. We therefore hypothesized that MV modulates  TLR2  expression and in turn modifies responsiveness to agonists such as bacterial lipopeptide (BLP).    Method  Both  in vitro  and  in vivo  experiments were conducted. First,  TLR2  expression and protein were measured in the A549 pulmonary epithelial cell line submitted to 8-hour cyclic stretch (20% elongation; 20/minute rate). After a 24-hour period of cyclic stretch, the inflammatory response of the A549 cells to the synthetic BLP, Pam 3 CSK 4 , was tested after 8 hours of exposure. In a second set of experiments, healthy anesthetized and paralyzed rabbits were submitted to 8-hour MV (tidal volume = 12 ml/kg, zero end-expiratory pressure; FIO 2  = 50%; respiratory rate = 20/minute) before being sacrificed for  TLR2  lung expression assessment. The lung inflammatory response to BLP was then tested in animals submitted to 24-hour MV before being sacrificed 8 hours after the tracheal instillation of Pam 3 CSK 4 .    Results  Cyclic stretch of human pulmonary epithelial cell lines increased both  TLR2  mRNA and protein expression. Cells submitted to cyclic stretch also increased IL-6 and IL-8 secretion in response to Pam 3 CSK 4 , a classical TLR2 ligand. A mild-stretch MV protocol induced a 60-fold increase of  TLR2  mRNA expression in lung tissue when compared with spontaneously breathing controls. Moreover, the combination of MV and airway exposure to Pam 3 CSK 4  acted synergistically in causing lung inflammation and injury.    Conclusions  Mild-stretch MV increases lung expression of  TLR2  and sensitizes the lung to bacterial TLR2 ligands. This may account for the propensity of mechanically ventilated patients to develop acute lung injury in the context of airway bacterial colonization/infection.

Mild-stretch mechanical ventilation upregulates toll-like receptor 2 and sensitizes the lung to bacterial lipopeptide