'Endothelial cells lining vascular
luminal surface represent an important site of signaling and injurious effects of
reactive oxygen species (ROS) produced by other cells and endothelium itself in
ischemia,
inflammation and other pathological conditions. Targeted delivery of ROS modulating
enzymes conjugated with
antibodies to endothelial surface molecules (vascular immunotargeting) provides site-specific interventions in the endothelial ROS, unattainable by other formulations including PEG-modified
enzymes. Targeting of ROS generating
enzymes (e.g.,
glucose oxidase) provides ROS- and site-specific models of endothelial oxidative stress, whereas targeting of
antioxidant enzymes SOD and
catalase offers site-specific quenching of
superoxide anion and H(2)O(2). These targeted
antioxidant interventions help to clarify specific role of endothelial ROS in vascular and pulmonary pathologies and provide basis for design of targeted
therapeutics for treatment of these pathologies. In particular, antibody/
catalase conjugates alleviate acute lung
ischemia/reperfusion injury, whereas antibody/SOD conjugates inhibit ROS-mediated vasoconstriction and inflammatory endothelial signaling. Encapsulation in
protease-resistant, ROS-permeable carriers targeted to endothelium prolongs protective effects of
antioxidant enzymes, further diversifying the means for targeted modulation of endothelial ROS.