Expression of Drosophila adenosine deaminase in immune cells during inflammatory response.

Expression of Drosophila adenosine deaminase in immune cells during inflammatory response.
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炎症反应期间,果蝇腺苷脱氨酶在免疫细胞中的表达。

DOI:
10.1371/journal.pone.0017741
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发表时间:
2011-03-11
期刊:
影响因子:
3.7
通讯作者:
Dolezal T
Dolezal T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Novakova M;Dolezal T

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细胞外腺苷是炎症反应的重要调节剂。它由胞外酶级联释放的ATP产生,并被腺苷脱氨酶(ADA)降解。有两种酶具有ADA活性:ADA 1和ADGF/ADA 2。ADA 2活性来源于巨噬细胞和树突状细胞,与人类和大鼠的炎症反应有关。果蝇具有六个ADGF蛋白家族,其中ADGF-A是幼虫期细胞外腺苷的主要调节剂。在这里,我们提出了一个ADGF-A表达的GFP报告基因的产生,通过使用同源重组的ADGF-A的编码序列与GFP的精确替换。我们表明,记者是专门表达的聚集血细胞(果蝇免疫细胞)形成黑色素囊,炎症反应的一个特点。因此,我们的重要报告证实了ADA在体内炎症部位的表达,并证明了在炎症反应期间对ADA活性的需求从昆虫到脊椎动物是进化保守的。我们的研究结果还表明,ADA活性是通过一个未知的转录后调控机制,特别是在炎症部位。利用各种突变体,诱导黑色素囊的形成,也是一个真实的免疫挑战提供的寄生蜂,我们表明,急性表达的ADGF-A蛋白不是由一个特定的信号级联,而是与免疫细胞的行为在一般的炎症反应。将ADGF-A在炎症部位的特异性表达与ADGF-A活性缺失时能量储存的释放联系起来,表明细胞外腺苷可能在免疫应答期间作为能量分配的信号,并且ADGF-A/ADA 2在这些炎症部位的表达可能调节这一作用。
Extra-cellular adenosine is an important regulator of inflammatory responses. It is generated from released ATP by a cascade of ectoenzymes and degraded by adenosine deaminase (ADA). There are two types of enzymes with ADA activity: ADA1 and ADGF/ADA2. ADA2 activity originates from macrophages and dendritic cells and is associated with inflammatory responses in humans and rats. Drosophila possesses a family of six ADGF proteins with ADGF-A being the main regulator of extra-cellular adenosine during larval stages. Herein we present the generation of a GFP reporter for ADGF-A expression by a precise replacement of the ADGF-A coding sequence with GFP using homologous recombination. We show that the reporter is specifically expressed in aggregating hemocytes (Drosophila immune cells) forming melanotic capsules; a characteristic of inflammatory response. Our vital reporter thus confirms ADA expression in sites of inflammation in vivo and demonstrates that the requirement for ADA activity during inflammatory response is evolutionary conserved from insects to vertebrates. Our results also suggest that ADA activity is achieved specifically within sites of inflammation by an uncharacterized post-transcriptional regulation based mechanism. Utilizing various mutants that induce melanotic capsule formation and also a real immune challenge provided by parasitic wasps, we show that the acute expression of the ADGF-A protein is not driven by one specific signaling cascade but is rather associated with the behavior of immune cells during the general inflammatory response. Connecting the exclusive expression of ADGF-A within sites of inflammation, as presented here, with the release of energy stores when the ADGF-A activity is absent, suggests that extra-cellular adenosine may function as a signal for energy allocation during immune response and that ADGF-A/ADA2 expression in such sites of inflammation may regulate this role.
DOI: 10.1002/cbic.200700057
发表时间: 2007-05-25
期刊: CHEMBIOCHEM
影响因子: 3.2
作者:
Rieder, Renate;Lang, Kathrin;Micura, Ronald
通讯作者: Micura, Ronald
DOI: 10.1006/bbrc.2000.2773
发表时间: 2000-06-07
影响因子: 3.1
作者:
Aldrich, MB;Blackburn, MR;Kellems, RE
通讯作者: Kellems, RE
DOI: 10.1073/pnas.0709951105
发表时间: 2008-07-22
影响因子: 11.1
作者:
Babcock, Daniel T.;Brock, Amanda R.;Galko, Michael J.
通讯作者: Galko, Michael J.
腺苷脱氨酶在果蝇幼虫发育中的作用。
DOI: 10.1371/journal.pbio.0030201
发表时间: 2005-07
期刊: PLOS BIOLOGY
影响因子: 9.8
作者:
Dolezal, Tomas;Dolezelova, Eva;Zurovec, Michal;Bryant, Peter J
通讯作者: Bryant, Peter J
DOI: 10.1074/jbc.271.23.13770
发表时间: 1996-06-07
影响因子: 4.8
作者:
Homma, K;Matsushita, T;Natori, S
通讯作者: Natori, S