Antioxidants Rescue Hyperoxia-induced
Suppression of Macrophage Phagocytosis of Pseudomonas
Aeruginosa
Lin Mantell, Department of
Pharmaceutical Sciences, College of Pharmacy and Allied Health
Professions
D. M. Morrow and T. Entezari Zaher,
Department of Pharmaceutical Sciences, College of Pharmacy and
Allied Health Professions and Cardiopulmonary Research, Feinstein
Institute for Medical Research at North Shore-LIJ Health
System
Abstract
Pseudomonas aeruginosa is one of the leading pathogens of
nosocomial pneumonia in patients receiving mechanical ventilation
with hyperoxia. High levels of reactive oxygen species generated
during exposure to hyperoxia may compromise bacterial clearance
through impairment of P. aeruginosa phagocytosis by alveolar
macrophages. This hypothesis was tested in both RAW 264.7
macrophages exposed to 95% O2 and alveolar macrophages from mice
exposed to >99% O2. Exposure to ≥95% O2 significantly diminished
phagocytosis of both mucoid and non-mucoid P. aeruginosa. To test
the effects of moderate hyperoxia on phagocytosis of P. aeruginosa,
both RAW cells and mice were exposed to 65% O2, which did not lead
to significant lung injury or marked inhibition of cell growth in
cultured macrophages. Intriguingly, however, exposure of either RAW
cells or mice to 65% O2, resulted in a drastic reduction in
phagocytosis of P. aeruginosa to a similar extent as that observed
at ≥95% O2. Hyperoxia-compromised phagocytosis of P. aeruginosa was
associated with disorganization of actin cytoskeleton, and could be
rescued by antioxidants, superoxide dismutase and procysteine.
Importantly, this normalization of the actin cytoskeleton was
accompanied by the restoration of bacterial phagocytosis. These
data suggest that antioxidants may effectively reduce the
occurrence of P. aeruginosa infection in ventilated patients.