Cyclic stretch of human lung cells induces an acidification and promotes bacterial growth

Am J Respir Cell Mol Biol. 2008 Mar;38(3):362-70. doi: 10.1165/rcmb.2007-0114OC. Epub 2007 Oct 5.


The reasons for bacterial proliferation in the lungs of mechanically ventilated patients are poorly understood. We hypothesized that prolonged cyclic stretch of lung cells influenced bacterial growth. Human alveolar type II-like A549 cells were submitted in vitro to prolonged cyclic stretch. Bacteria were cultured in conditioned supernatants from cells submitted to stretch and from control static cells. Escherichia coli had a marked growth advantage in conditioned supernatants from stretched A549 cells, but also from stretched human bronchial BEAS-2B cells, human MRC-5 fibroblasts, and murine RAW 264.7 macrophages. Stretched cells compared with control static cells acidified the milieu by producing increased amounts of lactic acid. Alkalinization of supernatants from stretched cells blocked E. coli growth. In contrast, acidification of supernatants from control cells stimulated bacterial growth. The effect of various pharmacological inhibitors of metabolic pathways was tested in this system. Treatment of A549 cells and murine RAW 264.7 macrophages with the Na(+)/K(+)-ATPase pump inhibitor ouabain during cyclic stretch blocked both the acidification of the milieu and bacterial growth. Several pathogenic bacteria originating from lungs of patients with ventilator-associated pneumonia (VAP) also grow better in vitro at slightly acidic pH (pH 6-7.2), pH similar to those measured in the airways from ventilated patients. This novel metabolic pathway stimulated by cyclic stretch may represent an important pathogenic mechanism of VAP. Alkalinization of the airways may represent a promising preventive strategy in ventilated critically ill patients.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis / etiology
  • Acidosis / metabolism*
  • Acidosis, Lactic / metabolism
  • Antimetabolites / pharmacology
  • Cell Line
  • Cell Survival / drug effects
  • Colony Count, Microbial
  • Culture Media, Conditioned / chemistry
  • Cyclic AMP / analysis
  • Deoxyglucose / pharmacology
  • Dose-Response Relationship, Drug
  • Epithelial Cells / cytology
  • Escherichia coli K12 / drug effects
  • Escherichia coli K12 / growth & development*
  • Formazans / metabolism
  • Glucose / analysis
  • Humans
  • Hydrogen-Ion Concentration
  • Lactates / analysis
  • Lactic Acid / antagonists & inhibitors
  • Lactic Acid / metabolism
  • Models, Biological
  • Ouabain / pharmacology
  • Oxamic Acid / pharmacology
  • Pneumonia, Ventilator-Associated / etiology
  • Pulmonary Alveoli / cytology*
  • Respiration, Artificial / adverse effects
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors
  • Stress, Mechanical
  • Time Factors


  • Antimetabolites
  • Culture Media, Conditioned
  • Formazans
  • Lactates
  • Lactic Acid
  • Ouabain
  • Deoxyglucose
  • Cyclic AMP
  • Sodium-Potassium-Exchanging ATPase
  • Glucose
  • Oxamic Acid