Abstract
The NOTCH pathway is a well-conserved signaling pathway that is believed to be engaged in several pathological processes in the lung, e.g. pulmonary arterial hypertension (PAH). In PAH it has been shown that a significant increase of perivascular numbers of inflammatory cells occur. Is NOTCH activation involved in their recruitment?
The aim of this study was to elucidate the role of the NOTCH signaling pathway in inducing migration of inflammatory cells by priming cells with JAG-1 and DLL-4.
Human monocytes, T-lymphocytes and dendritic cells were isolated from venous blood from healthy volunteers. For migration assays nitrocellulose membrane filters and a modified 48 well microchemotaxis chamber were used. Cells were preincubated with Notch ligands and pathway inhibitors at different concentrations for well-defined time periods. Cells were allowed to migrate against medium or fMLP in a humified atmosphere. The distance cells migrated was measured microscopically, and the “Chemotactic Index” (CI) was defined as the ratio between the distance cells migrated towards positive control and that towards medium.Both Notch ligands, JAG-1 and DLL-4 can induce migration after priming inflammatory cells with a maximum effect observed at a concentration of 100ng/ml. The effect observed after priming of cells was comparable with migration elicited by direct stimulation with the well-known chemoattractants fMLP (10-8 M) or MCP-1 (10-8 M).
The Notch signalling pathway can stimulate migration of human inflammatory cells in vitro. Priming of inflammatory cells with NOTCH ligands induces a significant migratory response in vitro. Consequently, the NOTCH pathway may serve as a new therapeutic target in future.
- Copyright ©ERS 2015
