Vitamin E attenuates P. aeruginosa‐mediated injury in pulmonary endothelial cells

Abstract

Infections caused by the opportunistic pathogen P. aeruginosa are a serious complication in critically ill patients with often lethal consequences. The high mortality of patients who develop P. aeruginosa pneumonia is associated with acute lung injury, characterized by airspace flooding. We have previously shown that in endothelial cells P. aeruginosa induces the small G‐protein RhoA, increasing actin stress fiber formation, and permeability. Herein, we hypothesize that the antioxidant vitamin, Vitamin E (Vit E) will be beneficial in preventing P. aeruginosa‐mediated damage. In rat microvascular endothelial cells (RMVEC), exposure to the PAK‐strain of P. aeruginosa (MOI 80 for 10 minutes), increased ROS production. This was completely prevented with pretreatment with 2 doses of Vit E, (18 and 1 hr prior to administration of PAK). Electric cell‐substrate impedance sensing (ECIS) was used as a functional assay to measure changes in resistance in confluent monolayers following exposure to PAK (MOI 80). PAK exposure decreased resistance indicating increased permeability. This decrease was attenuated by pretreatment with Vit E. RhoA activation and stress fiber formation by PAK was also completely blocked by pre‐treatment with Vit E. These data suggest a ROS‐component to PAK‐mediated damage and indicate a possible therapeutic role for Vit E.