Next Article in Journal
Immunohistochemical Expression of Aquaporin-1 in Fluoro-Edenite-Induced Malignant Mesothelioma: A Preliminary Report
Previous Article in Journal
D181A Site-Mutagenesis Enhances Both the Hydrolyzing and Transfructosylating Activities of BmSUC1, a Novel β-Fructofuranosidase in the Silkworm Bombyx mori
Article Menu
Issue 3 (March) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2018, 19(3), 684; https://doi.org/10.3390/ijms19030684

Loss of BID Delays FASL-Induced Cell Death of Mouse Neutrophils and Aggravates DSS-Induced Weight Loss

1
Institute of Pharmacology, University of Bern, 3010 Bern, Switzerland
2
Institute of Pathology, University of Bern, 3008 Bern, Switzerland
3
Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland
*
Author to whom correspondence should be addressed.
Received: 30 January 2018 / Revised: 21 February 2018 / Accepted: 25 February 2018 / Published: 28 February 2018
(This article belongs to the Special Issue Neutrophil: Regulation of Functional Activation and Survival)
Full-Text   |   PDF [2281 KB, uploaded 28 February 2018]   |  

Abstract

Neutrophils are key players in the early defense against invading pathogens. Due to their potent effector functions, programmed cell death of activated neutrophils has to be tightly controlled; however, its underlying mechanisms remain unclear. Fas ligand (FASL/CD95L) has been shown to induce neutrophil apoptosis, which is accelerated by the processing of the BH3-only protein BH3 interacting domain death agonist (BID) to trigger mitochondrial apoptotic events, and been attributed a regulatory role during viral and bacterial infections. Here, we show that, in accordance with previous works, mouse neutrophils underwent caspase-dependent apoptosis in response to FASL, and that this cell death was significantly delayed upon loss of BID. However, pan-caspase inhibition failed to protect mouse neutrophils from FASL-induced apoptosis and caused a switch to RIPK3-dependent necroptotic cell death. Intriguingly, such a switch was less evident in the absence of BID, particularly under inflammatory conditions. Delayed neutrophil apoptosis has been implicated in several auto-inflammatory diseases, including inflammatory bowel disease. We show that neutrophil and macrophage driven acute dextran sulfate sodium (DSS) induced colitis was slightly more aggravated in BID-deficient mice, based on significantly increased weight loss compared to wild-type controls. Taken together, our data support a central role for FASL > FAS and BID in mouse neutrophil cell death and further underline the anti-inflammatory role of BID. View Full-Text
Keywords: neutrophil; FAS/CD95; BID; apoptosis; RIPK3; necroptosis; caspases; inflammation; colitis; mouse model neutrophil; FAS/CD95; BID; apoptosis; RIPK3; necroptosis; caspases; inflammation; colitis; mouse model
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Wicki, S.; Gurzeler, U.; Corazza, N.; Genitsch, V.; Wong, W.W.-L.; Kaufmann, T. Loss of BID Delays FASL-Induced Cell Death of Mouse Neutrophils and Aggravates DSS-Induced Weight Loss. Int. J. Mol. Sci. 2018, 19, 684.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top