Exchange during HVT-ventilation as is the case in the induction of lung injury by LPS. It has been demonstrated that ventilator-induced mechanical stretch may also lead to the destabilization of alveolar-epithelial and capillary-endothelial barriers thereby resulting in increased vascular permeability and pulmonary edema. Ang-1 administration will probably influence the capillary-endothelial but not the alveolar-epithelial barrier since the Tie2 receptor is mainly expressed on endothelial cells. Thus, the possibility remains that Ang-1 treatment is not capable of restoring lung injury induced by HVT-ventilation as it only modulates endothelial inflammation. The fact that Ang-1 prevents pulmonary vascular leakage in animals exposed to LPS, which induces a generalized inflammation primarily in the endothelial cells of the lung, supports this hypothesis. Taken together, our data indicate that treatment with Ang-1 inhibits various aspects of VILI such as granulocyte infiltration, chemokine/cytokine and VEGF expression. However, Ang-1 treatment did not protect HVT-ventilated mice against the more crude parameters of VILI. In this respect, it is of interest that the TNF-a inhibitor Etanercept diminished inflammation and coagulation in the lungs of ventilated mice without influencing alveolar-capillary permeability and pulmonary edema, which is in line with our present results. We propose that Ang-1 should not be applied to combat the mechanosensitive aspects of ventilator-induced lung injury in critically ill patients. Nonetheless, treatment with Ang-1 may well be considered as an anti-inflammatory therapy when inflammation is the primary inducer of lung injury, like in nonventilated patients diagnosed with ALI/ARDS. Many microbial pathogens invade their human and animal hosts through the mucosal surfaces of the respiratory, gastrointestinal and urogenital tracts. Immunity at the mucosal surface would help prevent the pathogen from establishing and from disseminating to other organs to cause systemic disease. The majority of currently approved human/veterinary vaccines are Bortezomib administered systemically, and they fail to elicit effective mucosal immunity. The few mucosal vaccines currently in the marketplace are all based on the use of live-attenuated or dead pathogen cells. Although these vaccines are efficacious, there are lingering concerns regarding potential reversion to virulence, overall safety in immunocompromised populations, and the possible inclusion of toxic cell components such as endotoxins. Vaccines based on acellular or subunit antigens would be safer, but such antigens are generally poorly immunogenic on their own. This has sustained global research efforts at developing mucosal adjuvants and nonreplicating delivery systems such as detoxified cholera toxin and Escherichia coli heat labile toxin, CpG oligonucleotides, DNA, microparticulates such as virosomes, liposomes, cochleates, polymeric microspheres, and immunostimulating complexes such as ISCOMs.