Submitted on December 31, 2003
Accepted on July 21, 2004
Superoxide Dismutase Moderates Basal and Induced Bacterial Adherence and Interleukin-8 Expression in Airway Epithelial Cells
Yuko Arita1, Ansamma Joseph2, Hshi-chi Koo3, Yuchi Li2, Thomas A Palaia4, Jonathan M Davis5, and Jeffrey A Kazzaz6*
1 CardioPulmonary Research Institute, Mineola, NY, USA; Medicine (Divisions of Pulmonary and Critical Medicine and Nephrology), Winthrop-University Hospital, Mineola, NY, USA
2 CardioPulmonary Research Institute, Mineola, NY, USA; Thoracic and Cardiovascular Surgery, Winthrop-University Hospital, Mineola, NY, USA
3 CardioPulmonary Research Institute, Mineola, NY, USA; Pediatrics, Winthrop-University Hospital, Mineola, NY, USA
4 Medicine (Divisions of Pulmonary and Critical Medicine and Nephrology), Winthrop-University Hospital, Mineola, NY, USA
5 CardioPulmonary Research Institute, Mineola, NY, USA; Pediatrics, Winthrop-University Hospital, Mineola, NY, USA; SUNY Stony Brook School of Medicine, Stony Brook, NY, USA
6 CardioPulmonary Research Institute, Mineola, NY, USA; Medicine (Divisions of Pulmonary and Critical Medicine and Nephrology), Winthrop-University Hospital, Mineola, NY, USA; SUNY Stony Brook School of Medicine, Stony Brook, NY, USA
* To whom correspondence should be addressed. E-mail: jkazzaz{at}winthrop.org.
Bacterial infection of the tracheobronchial tree is a frequent, serious complication in patients receiving treatment with oxygen and mechanical ventilation, resulting in increased morbidity and mortality. Using human airway epithelial cell culture models, we examined the effect of hyperoxia on bacterial adherence and the expression of IL-8, an important mediator involved in the inflammatory process. A 24 h exposure to 95% O2increased P. aeruginosa (PA) adherence 57% in A549 cells (P <0.01) and 115% in 16HBE cells (P <0.01), but had little effect on S. aureus (SA) adherence. Exposure to hyperoxia, followed by a 1 h incubation with SA, further enhanced PA adherence (P<0.01) suggesting that hyperoxia and SA colonization may enhance the susceptibility of lung epithelial cells to gram-negative infections. IL-8 expression was also increased in cells exposed to both hyperoxia and PA. Stable or transient overexpression of mangenese superoxide dismutate (MnSOD) reduced both basal and stimulated levels of PA adherence and IL-8 levels in response to exposure to either hyperoxia or PA. These data indicate that hyperoxia increases susceptibility to infection and that the pathways are mediated by reactive oxygen species (ROS). Therapeutic intervention strategies designed to prevent accumulation of intracellular ROS may reduce opportunistic pulmonary infections.
