The effect of L-arginine and L-citrulline on NOx production in primary human airway epithelial cells exposed to asymmetric dimethylarginine (ADMA)

We determine: 1) whether the addition of asymmetric dimethylarginine (ADMA) reduces nitric oxide (NO)-related metabolites in primary airway epithelial cells under IL-13/ IFNγ stimulation, 2) supplementation of L-arginine/L-citrulline to cultures with high ADMA/iNOS expression is able to redirect iNOS towards NOx production. L-arginine and L-citrulline supplementation are able to increase the formation of NOx (nitrates + nitrates) in human airway epithelial cells, despite treatment with endogenous iNOS inhibitor ADMA. L-arginine and L-citrulline may have a therapeutic potential in diseases in which there is a defective production of NO

Selective Adsorption of Surfactant Lipids by Single-Walled Carbon Nanotubes in Mouse Lung upon Pharyngeal Aspiration

The pulmonary route represents one of the most important portals of entry for nanoparticles into the body. However, the in vivo interactions of nanoparticles with biomolecules of the lung have not been sufficiently studied. Here, using an established mouse model of pharyngeal aspiration of single-walled carbon nanotubes (SWCNTs), we recovered SWCNTs from the bronchoalveolar lavage fluid (BALf), purified them from possible contamination with lung cells, and examined the composition of phospholipids adsorbed on SWCNTs by liquid chromatography mass spectrometry (LC-MS) analysis. We found that SWCNTs selectively adsorbed two types of the most abundant surfactant phospholipids: phosphatidylcholines (PC) and phosphatidylglycerols (PG). Molecular speciation of these phospholipids was also consistent with pulmonary surfactant. Quantitation of adsorbed lipids by LC-MS along with the structural assessments of phospholipid binding by atomic force microscopy and molecular modeling indicated that the phospholipids (∼108 molecules per SWCNT) formed an uninterrupted "coating" whereby the hydrophobic alkyl chains of the phospholipids were adsorbed onto the SWCNT with the polar head groups pointed away from the SWCNT into the aqueous phase. In addition, the presence of surfactant proteins A, B, and D on SWCNTs was determined by LC-MS. Finally, we demonstrated that the presence of this surfactant coating markedly enhanced the in vitro uptake of SWCNTs by macrophages. Taken together, this is the first demonstration of the in vivo adsorption of the surfactant lipids and proteins on SWCNTs in a physiologically relevant animal model