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

Abstract

Background: A number of studies have demonstrated the effectiveness of liquid ventilation with perfluorocarbons in improving pulmonary function in acute respiratory distress syndrome. Although it is known that perfluorocarbon-associated gas exchange facilitates lung mechanics and oxygenation, the complete mechanism by which perfluorocarbons exert their beneficial effects in acute lung injury still remains unclear. Possibly, an influence of perfluorocarbons on proinflammatory and procoagulant features of monocytic cells present in the alveolar space, such as alveolar macrophages (AMs), may be involved. Therefore, we examined in an in vitro model the effects of perfluorocarbon on both activated mononuclear blood cells (MBCs) and AMs by monitoring the expression of interleukin (IL)-1β, tumor necrosis factor (TNF)α, 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 authors observed that perfluorohexane droplets were phagocytosed by activated monocytes as well as by in vitro-cultured AMs within 1-3 h. After lipopolysaccharide 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-1β and TNFα in the supernatant of lipopolysaccharidestimulated MBC was significantly 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 perfluorohexane 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 of role of liquid ventilation with perfloucarbons in injuries associated with local activation of inflammatory processes.