Interfacial Reactions of Ozone with Lipids and Proteins in a Model Lung Surfactant System

Abstract

Oxidative stresses from irritants such as hydrogen peroxide and ozone (O3) can cause dysfunction of the pulmonary surfactant (PS) in the human lung, resulting in chronic diseases of the respiratory tract. For identification of structural changes of major components of PS due to the heterogeneous reaction with O3, field induced droplet ionization (FIDI) mass spectrometry is utilized to probe the surfactant layer system. FIDI is a soft ionization method in which ions are extracted from the surface of micro liter volume droplets. We report the structurally specific oxidative changes of \(\textrm{SP-B}_{1-25}\) (a shortened version of human surfactant protein B) and 1-palmitoyl-2-oleoyl-sn-phosphatidylglycerol (POPG) due to reaction with O3 at the air-liquid interface. We also present studies of the interfacial oxidation of \(\textrm{SP-B}_{1-25}\) in a non-ionizable 1-palmitoyl-2-oleoyl-sn-glycerol monolayer as a model lung surfactant system, where the competitive oxidation of the two components is observed. Our results indicate that the heterogeneous reaction at the interface is different from that in the bulk phase. For example, we observe the hydroxyhydroperoxide and the secondary ozonide as major products of the heterogeneous ozonolysis of POPG. These products are metastable and difficult to observe in the bulk-phase. In addition, compared to the nearly complete homogeneous oxidation of \(\textrm{SP-B}_{1-25}\), only a subset of the amino acids known to react with ozone is oxidized in the hydrophobic interfacial environment. Combining these experimental observations with the results of molecular dynamics simulations provides an improved understanding of the interfacial structure and chemistry of a model lung surfactant system when subject to oxidative stress.