Perfluorochemical liquid-adenovirus suspensions enhance gene delivery to the distal lung.

WE COMPARED LUNG DELIVERY METHODS OF RECOMBINANT ADENOVIRUS (RAD): (1) rAd suspended in saline, (2) rAd suspended in saline followed by a pulse-chase of a perfluorochemical (PFC) liquid mixture, and (3) a PFC-rAd suspension. Cell uptake, distribution, and temporal expression of rAd were examined using A549 cells, a murine model using luciferase bioluminescence, and histological analyses. Relative to saline, a 4X increase in transduction efficiency was observed in A549 cells exposed to PFC-rAd for 2-4 h.

Superoxide dismutase attenuates hyperoxia-induced interleukin-8 induction via AP-1.

Exposure of lung epithelial cells to hyperoxia results in the generation of excess reactive oxygen species (ROS), cell damage, and production of proinflammatory cytokines (interleukin-8; IL-8). Although activation of the NF-kappaB and c-Jun N-terminal kinase (JNK)/activator protein (AP)-1 transcription pathways occurs in hyperoxia, it is unclear whether activation of the AP-1 pathway has a direct impact on IL-8 production and whether overexpression of superoxide dismutase (SOD) can mitigate these proinflammatory processes. A549 cells were exposed to 95% O(2), and ROS production, AP-1 activation, and IL-8 levels were determined.

Antioxidants improve antibacterial function in hyperoxia-exposed macrophages.

Hyperoxia and pulmonary infections are well known to increase the risk of acute and chronic lung injury in newborn infants, but it is not clear whether hyperoxia directly increases the risk of pneumonia. The purpose of this study was to examine: (1) the effects of hyperoxia and antioxidant enzymes on inflammation and bacterial clearance in mononuclear cells and (2) developmental differences between adult and neonatal mononuclear cells in response to hyperoxia. Mouse macrophages were exposed to either room air or 95% O2 for 24 h and then incubated with Pseudomonas aeruginosa.

Perfluorochemical liquids enhance delivery of superoxide dismutase to the lungs of juvenile rabbits.

Previous studies suggest acute lung injury (ALI) in premature newborns is associated with relative deficiency of antioxidant enzymes that may be ameliorated by recombinant human superoxide dismutase (rhSOD). Perfluorochemicals (PFCs) are distributed homogeneously and support gas exchange in diseased lungs. We investigated whether PFCs could provide an effective delivery system for rhSOD.

Mitochondrial localization of catalase provides optimal protection from H2O2-induced cell death in lung epithelial cells.

Reactive oxygen species (ROS) can cause cell injury and death via mitochondrial-dependent pathways, and supplementation with antioxidants has been shown to ameliorate these processes. The c-Jun NH(2)-terminal kinase (JNK) pathway has been shown to play a critical role in ROS-induced cell death. To determine if targeting catalase (CAT) to the mitochondria provides better protection than cytosolic expression against H(2)O(2)-induced injury, the following two approaches were taken: 1) adenoviral-mediated transduction was performed using cytosolic (CCAT) or mitochondrial (MCAT) CAT cDNAs and 2) stable cell lines were generated overexpressing CAT in mitochondria (n = 3).

Effects of transgene expression of superoxide dismutase and glutathione peroxidase on pulmonary epithelial cell growth in hyperoxia.

Prolonged exposure to supraphysiological oxygen concentrations results in the generation of reactive oxygen species, which can cause significant lung injury in critically ill patients. Supplementation with human recombinant antioxidant enzymes (AOE) may mitigate hyperoxic lung injury, but it is unclear which combination and concentration will optimally protect pulmonary epithelial cells. First, stable cell lines were generated in alveolar epithelial cells (MLE12) overexpressing one or more of the following AOE: Mn superoxide dismutase (MnSOD), CuZnSOD, or glutathione peroxidase 1.

Superoxide dismutase moderates basal and induced bacterial adherence and interleukin-8 expression in airway epithelial cells.

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 interleukin-8 (IL-8), an important mediator involved in the inflammatory process. A 24-h exposure to 95% O(2) increased Pseudomonas aeruginosa (PA) adherence 57% in A549 cells (P < 0.

Inhibition of c-Jun N-terminal kinase pathway improves cell viability in response to oxidant injury.

Oxidant insults can lead to apoptotic and nonapoptotic cell death. Lung epithelial cells exposed to high levels of oxygen do not die via apoptosis, but through a much slower, morphologically distinct process involving cell and nuclear swelling. In contrast, H2O2 induces a rapid apoptotic cell death.

Safety and efficacy of intratracheal recombinant human Clara cell protein in a newborn piglet model of acute lung injury.

Despite the widespread use of exogenous surfactant, acute and chronic lung injury continues to be a major cause of morbidity in preterm infants. CC10 is a protein produced by Clara cells that inhibits phospholipase A2 and has anti-inflammatory and antifibrotic properties. We studied whether intratracheal (IT) recombinant human Clara cell protein (rhCC10) could safely minimize lung injury in a newborn piglet model of acute lung injury.