Perfluorohexane attenuates proinflammatory and procoagulatory response of activated monocytes and alveolar macrophages

Background: A number of studies have demonstrated the effectiveness of liqu id ventilation with perfluorocarbons in improving pulmonary function in acu te respiratory distress syndrome. Although it is known that perfluorocarbon -associated gas exchange facilitates lung mechanics and oxygenation, the co mplete mechanism by which perfluorocarbons exert their beneficial effects i n acute lung injury still remains unclear. Possibly, an influence of perflu orocarbons on proinflammatory and procoagulant features of monocytic cells present in the alveolar space, such as alveolar macrophages (AMs), may be i nvolved. Therefore, we examined in an in vitro model the effects of perfluo rocarbon on both activated mononuclear blood cells (MBCs) and AMs by monito ring the expression of interleukin (IL)-1 beta, tumor necrosis factor (TNF) alpha, and tissue factor (TF). Methods: Mononuclear blood cells, obtained from peripheral blood of healthy volunteers, or AMs from diagnostic bronchoalveolar lavage were stimulated by incubation with Lipopolysaccharide in the presence of different amounts of perfluorohexane, which was devoid of cytotoxicity. Results: Using both video-enhanced contrast and electron microscopy, the au thors observed that perfluorohexane droplets were phagocytosed by activated monocytes as web as by in vitro-cultured AMs within 1-3 h. After lipopolys accharide stimulation of monocytes or AMs, we observed a down-regulation of TF mRNA and a significant inhibition (P < 0.05) of cellular TF antigen by perfluorohexane. In addition, the concentration of both IL-1<beta> and TNF alpha in the supernatant of lipopolysaccharide-stimulated MBC was significa ntly decreased (P < 0.01) by perfluorohexane compared with controls without perfluorohexane. By preincubation of lipopolysaccharide-containing medium with perfluorohexane, the authors could exclude that the inhibitory effect of perfluorohexane was caused by binding or sequestering limited amounts of Lipopolysaccharide. Conclusion: Taken together, our results demonstrate an interference of perf luorohexane with the expression of the procoagulant protein TF on monocytes and AMs as well as with the release of proinflammatory cytokines by MBCs. These effects may contribute to the protective role of liquid ventilation w ith perfluorocarbons in injuries associated with local activation of inflam matory processes.