Cargando…
Accelerated Apoptosis of Neutrophils in Familial Mediterranean Fever
The causative mutations for familial Mediterranean fever (FMF) are located in the MEFV gene, which encodes pyrin. Pyrin modulates the susceptibility to apoptosis via its PYD domain, but how the mutated versions of pyrin affect apoptotic processes are poorly understood. Spontaneous and induced rates...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4435041/ https://www.ncbi.nlm.nih.gov/pubmed/26042122 http://dx.doi.org/10.3389/fimmu.2015.00239 |
_version_ | 1782371840280231936 |
---|---|
author | Manukyan, Gayane Aminov, Rustam Hakobyan, Gagik Davtyan, Tigran |
author_facet | Manukyan, Gayane Aminov, Rustam Hakobyan, Gagik Davtyan, Tigran |
author_sort | Manukyan, Gayane |
collection | PubMed |
description | The causative mutations for familial Mediterranean fever (FMF) are located in the MEFV gene, which encodes pyrin. Pyrin modulates the susceptibility to apoptosis via its PYD domain, but how the mutated versions of pyrin affect apoptotic processes are poorly understood. Spontaneous and induced rates of systemic neutrophil apoptosis as well as the levels of proteins involved in apoptosis were investigated ex vivo in patients with FMF using flow cytometry and RT-qPCR. The freshly collected neutrophils from the patients in FMF remission displayed a significantly larger number of cells spontaneously entering apoptosis compared to control (6.27 ± 2.14 vs. 1.69 ± 0.18%). This elevated ratio was retained after 24 h incubation of neutrophils in the growth medium (32.4 ± 7.41 vs. 7.65 ± 1.32%). Correspondingly, the mRNA level for caspase-3 was also significantly increased under these conditions. In response to the inducing agents, the neutrophils from FMF patients also displayed significantly elevated apoptotic rates compared to control. The elevated rates, however, can be largely explained by the higher basal ratio of apoptotic cells in the former group. Monitoring of several proteins involved in apoptosis has not revealed any conventional mechanisms contributing to the enhanced apoptotic rate of neutrophils in FMF. Although the exact molecular mechanisms of accelerated neutrophil apoptosis in FMF remain unknown, it may provide a protection against excessive inflammation and tissue damage due to a massive infiltration of neutrophils in the acute period of the disease. |
format | Online Article Text |
id | pubmed-4435041 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-44350412015-06-03 Accelerated Apoptosis of Neutrophils in Familial Mediterranean Fever Manukyan, Gayane Aminov, Rustam Hakobyan, Gagik Davtyan, Tigran Front Immunol Immunology The causative mutations for familial Mediterranean fever (FMF) are located in the MEFV gene, which encodes pyrin. Pyrin modulates the susceptibility to apoptosis via its PYD domain, but how the mutated versions of pyrin affect apoptotic processes are poorly understood. Spontaneous and induced rates of systemic neutrophil apoptosis as well as the levels of proteins involved in apoptosis were investigated ex vivo in patients with FMF using flow cytometry and RT-qPCR. The freshly collected neutrophils from the patients in FMF remission displayed a significantly larger number of cells spontaneously entering apoptosis compared to control (6.27 ± 2.14 vs. 1.69 ± 0.18%). This elevated ratio was retained after 24 h incubation of neutrophils in the growth medium (32.4 ± 7.41 vs. 7.65 ± 1.32%). Correspondingly, the mRNA level for caspase-3 was also significantly increased under these conditions. In response to the inducing agents, the neutrophils from FMF patients also displayed significantly elevated apoptotic rates compared to control. The elevated rates, however, can be largely explained by the higher basal ratio of apoptotic cells in the former group. Monitoring of several proteins involved in apoptosis has not revealed any conventional mechanisms contributing to the enhanced apoptotic rate of neutrophils in FMF. Although the exact molecular mechanisms of accelerated neutrophil apoptosis in FMF remain unknown, it may provide a protection against excessive inflammation and tissue damage due to a massive infiltration of neutrophils in the acute period of the disease. Frontiers Media S.A. 2015-05-18 /pmc/articles/PMC4435041/ /pubmed/26042122 http://dx.doi.org/10.3389/fimmu.2015.00239 Text en Copyright © 2015 Manukyan, Aminov, Hakobyan and Davtyan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Manukyan, Gayane Aminov, Rustam Hakobyan, Gagik Davtyan, Tigran Accelerated Apoptosis of Neutrophils in Familial Mediterranean Fever |
title | Accelerated Apoptosis of Neutrophils in Familial Mediterranean Fever |
title_full | Accelerated Apoptosis of Neutrophils in Familial Mediterranean Fever |
title_fullStr | Accelerated Apoptosis of Neutrophils in Familial Mediterranean Fever |
title_full_unstemmed | Accelerated Apoptosis of Neutrophils in Familial Mediterranean Fever |
title_short | Accelerated Apoptosis of Neutrophils in Familial Mediterranean Fever |
title_sort | accelerated apoptosis of neutrophils in familial mediterranean fever |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4435041/ https://www.ncbi.nlm.nih.gov/pubmed/26042122 http://dx.doi.org/10.3389/fimmu.2015.00239 |
work_keys_str_mv | AT manukyangayane acceleratedapoptosisofneutrophilsinfamilialmediterraneanfever AT aminovrustam acceleratedapoptosisofneutrophilsinfamilialmediterraneanfever AT hakobyangagik acceleratedapoptosisofneutrophilsinfamilialmediterraneanfever AT davtyantigran acceleratedapoptosisofneutrophilsinfamilialmediterraneanfever |