The anti-apoptotic Bcl-2 family protein A1/Bfl-1 regulates neutrophil survival and homeostasis and is controlled via PI3K and JAK/STAT signaling

Cell Death & Disease
J VierS Kirschnek

Abstract

Neutrophil granulocytes are innate effector cells of the first line of defense against pyogenic bacteria. Neutrophil lifespan is short, is prolonged by pro-inflammatory stimuli, controls functionality of the cells and can determine tissue damage. Experimental analysis of primary neutrophils is difficult because of their short lifespan and lack of possibilities of genetic manipulation. The Hoxb8 system of neutrophil differentiation from immortalized progenitor cells offers the advantage of unlimited production of neutrophils in vitro as well as easy genetic modification. We here use this system to analyze the role of the poorly characterized anti-apoptotic B-cell lymphoma protein 2 (Bcl-2) family member A1/Bfl-1 (Bcl-2-related protein A1) for survival and homeostasis of neutrophils and of neutrophil progenitors. Low constitutive mRNA and protein expression of A1 was detected, while A1 was transiently upregulated early during differentiation. Pro-inflammatory stimuli caused strong, mainly transcriptional, A1 upregulation, in contrast to posttranscriptional regulation of Mcl-1 (induced myeloid leukemia cell differentiation protein). Inhibitor studies showed that phosphoinositide-3 kinase (PI3K)/Akt and Janus kinase (JAK)/signal tr...Continue Reading

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Dec 22, 2017·PLoS Pathogens·Christina GavegnanoRafick Pierre Sékaly
Feb 1, 2018·Journal of Animal Science·Kiah M GourleyRobert D Goodband
Jan 4, 2018·Blood Advances·Yi ZengEmmanuel Katsanis
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Feb 26, 2020·The Journal of Experimental Medicine·Cynthia LouisIan P Wicks
Sep 5, 2020·Molecular Carcinogenesis·Zina SarifJürgen Eberle
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May 26, 2021·European Journal of Medicinal Chemistry·Xue LiZhengyu Jiang
Jul 3, 2021·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Liang WangDapeng Chen
Aug 13, 2021·Cell Death & Disease·Constanze KurschatGeorg Häcker

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Methods Mentioned

BETA
genetic modification
ubiquitination
density gradient centrifugation
flow cytometry

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