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

Abstract

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.

Toll-like receptors: a link between mechanical ventilation, innate immunity and lung injury?

“…MV can deeply alter this flimsy equilibrium by inducing inappropriate TLR expression. All these data add new insights into the underlying mechanisms by which MV promotes bacterial growth and injury within the lung [21][22][23].…”

Carbon Dioxide in the Critically Ill: Too Much or Too Little of a Good Thing?

“…Specifically, acidification of culture mediums to pH 7.20 enhances the growth of Escherichia coli, and this effect has been demonstrated across several species of bacteria. 25,26 Whether treatment with appropriate antibiotics mitigates this effect in sepsis remains controversial. 25,27 …”

Pediatric Airway Maintenance and Clearance in the Acute Care Setting: How To Stay Out of Trouble

“…In fact, the cyclic stretch of alveolar epithelial cells may activate not only inflammatory mediators but also ion channels and pumps. 21 Given the possible prognostic relationship between exhaled-breath-condensate pH and clinical symptoms, it is quite plausible that exhaledbreath-condensate pH can prove useful in various clinical settings, including airway clearance. For example, if exhaled-breath-condensate pH falls prior to the onset of clinical symptoms, it is probably useful as an early marker, heralding the onset of various inflammatory lung diseases.…”

“…For example, if exhaled-breath-condensate pH falls prior to the onset of clinical symptoms, it is probably useful as an early marker, heralding the onset of various inflammatory lung diseases. Specifically, exhaled-breath-condensate pH could be used as a safe, noninvasive screening or preventive tool for ventilator-associated pneumonia (VAP), 21 or possibly impaired ciliary motility. Changes in exhaled-breath-condensate pH might also mark the progression or resolution of disease (eg, alerting clinicians to possible libration from mechanical ventilation).…”

“…[22][23][24][25][26][27][28][29][30][31] These negative implications include, but are not limited to, epithelial dysfunction, impaired ciliary motility, 32 bronchoconstriction, 23 altered mucus viscosity, inhibition of apoptosis of inflammatory cells, 33 enhanced bacterial attachment to epithelium, possibly fostering the development of VAP, 21 and augmented cellular inflammation. 15,17 Yet we pay little attention to this finding during routine airway clearance and maintenance.…”