TY - JOUR T1 - Human T-lymphocytes are affected by notch ligands in vitro JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - 4837 AU - Thomas Zöggeler AU - Kathrin Watzinger AU - Christian Kähler Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/4837.abstract N2 - Notch signaling is believed to be engaged in the pathophysiology of lung cancer and PAH. More recently, a significant increase of the perivascular number of T cells, cytotoxic T cells (CD8) and helper T cells (CD4) in vessels of IPAH lungs was shown. The aim of this study was to uncover, which influence the Notch-signaling pathway has on the migratory behaviour of human T-cells, in vitro.T-cells were isolated from EDTA-anticoagulated venous blood, taken from healthy donors. The isolation was carried out according to a standardized MACS protocol. For chemotaxisexperiments, a microchemotaxis chamber was used. Freshly isolated T-cells migrated through a 5µm pore sized cellulose membrane filter for 90 min in a humidified atmosphere. Migration depth of the cells in the filter was quantified microscopically by measuring the distance from the surface of the filters to the leading front of the cells. Blocking experiments were performed with the metalloprotease ADAM17.DLL4 and Jag1 significantly stimulated migration of T cells in a dose-dependent manner, revealing a maximal effect at 100ng/ml. Also preincubation with the Notch ligands for different time periods revealed a time dependent stimulation of migration. The maximal migratory response was observed after preincubation for 5 min. ADAM 17 significantly inhibited the migration of both human CD4+ and CD8+ T-cells towards DLL4 and Jag1 in a dose-dependent manner, revealing a maximal inhibition at 10-4 M.T cells may play a key role in the pathogenesis of pulmonary hypertension. Our data suggest a role for the Notch pathway in eliciting migration of T cells to areas of inflammation in the lung. Targeting this pathway may be a promising target in the near future. ER -