Platelets induce apoptosis via membrane-bound FasL
- Author(s)
- Schleicher, RI; Reichenbach, F; Kraft, P; Kumar, A; Lescan, M; Todt, F; Gobel, K; Hilgendorf, I; Geisler, T; Bauer, A; Olbrich, M; Schaller, M; Wesselborg, S; O'Reilly, L; Meuth, SG; Schulze-Osthoff, K; Gawaz, M; Li, X; Kleinschnitz, C; Edlich, F; Langer, HF;
- Details
- Publication Year 2015-09-17,Volume 126,Issue #12,Page 1483-1493
- Journal Title
- Blood
- Publication Type
- Journal Article
- Abstract
- After tissue injury, both wound sealing and apoptosis contribute to restoration of tissue integrity and functionality. Although the role of platelets for wound closure and induction of regenerative processes is well established, the knowledge about their contribution to apoptosis is incomplete. Here, we show that platelets present the death receptor Fas ligand (FasL) on their surface after activation. Activated platelets as well as the isolated membrane fraction of activated platelets but not of resting platelets induced apoptosis in a dose-dependent manner in primary murine neuronal cells, human neuroblastoma cells and mouse embryonic fibroblasts (MEFs). Membrane protein from platelets lacking membrane-bound FasL (FasLDeltam/Deltam) failed to induce apoptosis. Bax/Bak-mediated mitochondrial apoptosis signaling in target cells was not required for platelet-induced cell death, but increased the apoptotic response to platelet-induced Fas signaling. In vivo, platelet depletion significantly reduced apoptosis in a stroke model and an inflammation-independent model of N-methyl-D-aspartic acid (NMDA)-induced retinal apoptosis. Furthermore, experiments using platelet specific PF4Cre+ FasLfl/fl mice demonstrated a role of platelet-derived FasL for tissue apoptosis. Since apoptosis secondary to injury prevents inflammation, our findings describe a novel mechanism how platelets contribute to tissue homeostasis.
- Publisher
- ASH
- Research Division(s)
- Molecular Genetics Of Cancer
- PubMed ID
- 26232171
- Link To PubMed Central Version
- http://www.ncbi.nlm.nih.gov.ezp/pmc/articles/PMC4573871/
- Publisher's Version
- https://doi.org/10.1182/blood-2013-12-544445
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2015-08-21 12:29:32
Last Modified: 2015-12-18 09:41:12