Interfacial transfer of nitrogen dioxide and ozone is modulated by surfactant phospholipid films

Nitrogen dioxide (NO₂) and ozone (O₃) produce a broad range of pathologic and physiologic effects on the lung. Absorption of inhaled NO₂ and O₃ is coupled to near interfacial reactions between the solute gas and constituents of the airway and alveolar epithelial lining fluid (surfactant); a process termed “reactive absorption”. Alveolar surfactant imparts limited resistance to normal gas exchange compared to that contributed by either the pulmonary membrane (1/D_m) or uptake into red cells (1/&thetas; V_c). However, previous experimental evidence suggests that the physicochemical characteristics of the gas/liquid interface may influence the flux of molecules between the gas and aqueous phases. Based on these observations, we investigated whether monolayers of surface active phospholipids alter the interfacial flux of NO₂ and O₃, and furthermore, whether monolayer-induced resistance to flux could modulate exposure induced cytotoxicity in vitro. For evaluating monolayer effects on gas absorption we utilized an in vitro exposure apparatus that permitted variable compression of deposited phospholipid films, continuous measurement of surface tension, and determination of absorption rates. Films were deposited onto aqueous solutions in the absence or presence of absorption substrates and uptake was determined based on the mass balance across the exposure system. The results suggest that compressed monolayers enriched in dipalmitoyl phosphatidylcholine present significant resistance to NO₂ and O₃ absorption even at surface tensions greater than those achieved in vivo. In addition our results suggest that monolayer-induced resistance to gas flux is related to physico-chemical properties of the film itself rather than alterations within the aqueous and gas phases. For cell exposure studies, monolayers of fetal lung fibroblasts were exposed to O₃ and cytotoxicity evaluated following a post exposure recovery period using fluorescence microscopy. Results from these studies suggest that cytotoxicity is substantially reduced in the presence of interfacial DPPC. Furthermore these studies confirmed previous observations that the thickness of the aqueous phase overlaying cells during exposure plays a critical role in dosing. On the basis of these findings we propose that pulmonary surfactant may influence the intrapulmonary gas phase distribution of inhaled oxidant gases.