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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...

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Autores principales: Manukyan, Gayane, Aminov, Rustam, Hakobyan, Gagik, Davtyan, Tigran
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
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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.
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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
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AT hakobyangagik acceleratedapoptosisofneutrophilsinfamilialmediterraneanfever
AT davtyantigran acceleratedapoptosisofneutrophilsinfamilialmediterraneanfever