TY - JOUR T1 - The migration of monocytes is stimulated by Jagged-1 and DLL-4 via the notch pathway JF - European Respiratory Journal JO - Eur Respir J VL - 42 IS - Suppl 57 SP - P3875 AU - Kathrin Watzinger AU - Susanna Desole AU - Kaehler Christian Y1 - 2013/09/01 UR - http://erj.ersjournals.com/content/42/Suppl_57/P3875.abstract N2 - The notch signaling system is a highly conserved signaling system that functions to regulate tissue homoeostasis and morphogenesis of stem cells in adults. Monocytes serve as key cells in inflammatory and immunological processes.Monocytes were isolated from EDTA anticoagulated venous blood. For the chemotactic assays modified 48-well microchemotaxis chambers were used. Monocytes migrated through an 5 µm pore sized cellulose membrane filter for 45 min in a humified atmosphere against a gradient of the substances tested (fMLP, Jagged1, DLL4,DAPT). For blocking experiments monocytes were preincubated with specific ligands for different durations. Migration depth of the cells in the filter was quantified microscopically by measuring the distance [µm] from the surface of the filters to the leading front of the cells.The notch ligands DLL4 and Jagged1 significantly stimulate migration in a dose dependent manner revealing a maximal effect at [100ng/ml]. The effect was comparable with maximal stimulation of migration elicited by the well known chemoattractant fMLP (10-8 M). A significant inhibition of migration was observed by pre-incubating the cells with the γ-secretase inhibitor DAPT [10-4]. Interestingly, priming of cells with the ligands also elicited monocyte migration [maximal effect at 100ng/ml]. Different preincubation times with the ligands revealed that at least a preincubation time of 30 min is necessary to stimulate monocyte migration.Jagged1 and DLL4 directly stimulate migration of human monocytes in vitro. For activation of migration a cell-cell interaction for about 30 min seems to be necessary. In conclusion, it can be suggested, that Jagged1 DLL4 are involved in inflammatory processes. ER -