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Cyclic Stretch of Human Lung Cells Induces an Acidification and Promotes Bacterial Growth

¹ Intensive Care, University Hospitals of Geneva, and Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland

Correspondence and requests for reprints should be addressed to Jérôme Pugin, M.D., Soins Intensifs, Hôpitaux Universitaires de Genève, 1211 Genève 14, Switzerland. E-mail: jerome.pugin{at}medecine.unige.ch

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.

Key Words: ventilator-associated pneumonia • lactic acidosis • sodium pumps • pulmonary epithelial cells • cyclic stretch

CLINICAL RELEVANCE Cyclic stretch of human lung cells induces an acidification of the milieu, which promotes bacterial growth. This may represent an important pathophysiologic mechanism for the development of ventilator-associated pneumonia.