Foerster, A., Grotha, S. P., Seeger, J. M., Rabenhorst, A., Gehring, M., Raap, U., Letard, S., Dubreuil, P., Kashkar, H., Walczak, H., Roers, A. and Hartmann, K. (2015). Activation of KIT modulates the function of tumor necrosis factor-related apoptosis-inducing ligand receptor (TRAIL-R) in mast cells. Allergy, 70 (7). S. 764 - 775. HOBOKEN: WILEY. ISSN 1398-9995
Full text not available from this repository.Abstract
BackgroundMastocytosis is characterized by the accumulation of mast cells (MCs) associated with activating mutations of KIT. Tumor necrosis factor-related apoptosis-inducing ligand receptors (TRAIL-Rs) are preferentially expressed on neoplastic cells and induce the extrinsic apoptotic pathway. Recent studies reported on the expression of TRAIL-Rs and TRAIL-induced apoptosis in cultured human MCs, which depend on stem cell factor (SCF)-induced or constitutive KIT activation. Material and methodsWe sought to further define the impact of TRAIL-Rs on MCs in vivo and in vitro. Using Cre/loxP recombination, we generated mice with MC-specific and ubiquitous knockout of TRAIL-R. In these mice, anaphylaxis and numbers of MCs were investigated. We also explored the expression and function of TRAIL-Rs in cultured murine and human MCs upon activation of KIT. By conducting immunofluorescence staining, we analyzed the expression of TRAIL-Rs in MCs infiltrating the bone marrow of patients with mastocytosis. ResultsMC-specific deletion of TRAIL-R was associated with a slight, but significant increase in anaphylaxis. Numbers of MCs in MC-specific knockouts of TRAIL-R were comparable to controls. Whereas cultured IL-3-dependent murine MCs from wild-type mice were resistant to TRAIL-induced apoptosis, SCF-stimulated MCs underwent apoptosis in response to TRAIL. Interestingly, activating KIT mutations also promoted sensitivity to TRAIL-mediated apoptosis in human MCs. In line with these findings, MCs infiltrating the bone marrow of patients with mastocytosis expressed TRAIL-R1. ConclusionsActivation of KIT regulates the function of TRAIL-Rs in MCs. TRAIL-R1 may represent an attractive diagnostic and therapeutic target in diseases associated with KIT mutations, such as mastocytosis.
| Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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| URN: | urn:nbn:de:hbz:38-399831 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| DOI: | 10.1111/all.12612 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Journal or Publication Title: | Allergy | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Volume: | 70 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Number: | 7 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Page Range: | S. 764 - 775 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Date: | 2015 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Publisher: | WILEY | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Place of Publication: | HOBOKEN | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| ISSN: | 1398-9995 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Language: | English | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Faculty: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Divisions: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Subjects: | no entry | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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| URI: | http://kups.ub.uni-koeln.de/id/eprint/39983 |
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