498 Intratracheal Perfluorocarbons Alter TNFα and VEGF Expression in AT-II Cells During PMA-Induced Systemic Inflammation

Background: 20-40% of extremely preterm infants develop BPD. Besides “relative” hyperoxia, inflammation is a major contributor to the pathogenesis of BPD. Perfluorocarbons (PFC) can reduce oxidative stress and have anti-inflammatory properties. Until now the mechanism of PFC action on cellular level is not completely understood. The aim of this study was to elucidate the impact of PFC on Alveolar type II (AT-II) cells in vivo in an animal model of inflammation-induced BPD. Methods: Newborn rats received 500μg/kg bodyweight Phorbol 12-Myristate 13-Acetate (PMA) intraperitoneally and either air ( PMA/air ) or 50μl Perfluorodecalin ( PMA/PFD ) intratracheally. Healthy control animals were injected intraperitoneally with 0.2% DMSO ( Control ). After 24h AT-II-cells were isolated. I.) Proportion of TNFα- positive cells was assessed by fluorescence-immunocytochemistry. II.) Expression of TNFα, VEGF and VEGFR1 was analysed using real-time PCR. Data arise from 3 independent experiments. Results: I.) 37±2.3% of AT-II-cells showed TNFα- positive staining in the PMA/air group. In the PMA/ PFD group 22.3±4.0% of AT-II-cells were TNFα- positive (p=0.01) ( Control 16±1.5%). II.) Compared to Control, TNFα expression in the PMA/air group was 2.8-fold higher ( PMA/PFD group 1.1-fold). Expression of VEGF in PMA/air was 0.8-fold, in PMA/PFC 0.3-fold of Control . Expression of VEGFR1 in PMA/air was 1.6-fold, in PMA/PFC 2.7- fold higher than in Control . Conclusion: PMA-induced systemic inflammation leads to an increase of TNFα Protein and mRNA in AT-II-cells, which can be diminished by intratracheal application of PFC. Reduced expression of VEGF in AT-II-cells during inflammation was not restored by PFC, but may be compensated by the higher VEGFR1 expression.