Identification of macrophage extracellular trap-like structures in mammary gland adipose tissue: a preliminary study.
Identification of macrophage extracellular trap-like structures in mammary gland adipose tissue: a preliminary study.
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DOI：
10.3389/fimmu.2013.00067
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发表时间：
2013
影响因子：
7.3
通讯作者：
Coonrod SA
中科院分区：
文献类型：
--
作者：
Mohanan S;Horibata S;McElwee JL;Dannenberg AJ;Coonrod SA
先前已发现PAD 4介导的组蛋白H4精氨酸3（H4R3）的高瓜氨酸水平促进炎症组织中神经元细胞外陷阱的形成，并且认为由此产生的组蛋白H4瓜氨酸3（H4Cit3）修饰通过促进染色质解凝聚在细胞外陷阱（ET）形成中发挥关键作用。除了嗜中性粒细胞，巨噬细胞最近也被发现产生功能性细胞外陷阱（MET）。然而，PAD在巨噬细胞中ET形成中的作用先前尚未描述。在成熟的巨噬细胞中发现了PAD 2和PAD 4的转录物，这些细胞可以被诱导为瓜氨酸蛋白，从而提高了PAD可能通过组蛋白高瓜氨酸在巨噬细胞中的ET形成中发挥直接作用的可能性。在来自肥胖患者的乳房和内脏白色脂肪组织中，经常看到浸润性巨噬细胞包围死亡的脂肪细胞，形成特征性的“冠状结构”（CLS），并且这些病变的存在与炎症介质水平的增加相关。鉴于这些观察结果，我们已经开始研究以测试PAD是否在CLS巨噬细胞中表达以及这些巨噬细胞是否可能形成MET。我们的初步研究结果表明，PAD 2（和在较小程度上，PAD 4）在巨噬细胞系（RAW 264.7）和CLS病变中表达。此外，我们提供的证据表明，巨噬细胞衍生的细胞外组蛋白被视为周围假定的巨噬细胞内CLS病变，这些组蛋白含有H4Cit3修饰。这些初步发现支持我们的假设，即肥胖诱导的脂肪组织炎症通过PAD介导的组蛋白高瓜氨酸酶促进CLS病变内MET的形成。后续研究正在进行中，以进一步验证这些发现，并研究PAD介导的MET形成在乳腺CLS功能中的作用。
PAD4-mediated hypercitrullination of histone H4 arginine 3 (H4R3) has been previously found to promote the formation of Neutrophil Extracellular Traps in inflamed tissues and the resulting histone H4 citrulline 3 (H4Cit3) modification is thought to play a key role in extracellular trap (ET) formation by promoting chromatin decondensation. In addition to neutrophils, macrophages have also recently been found to generate functional extracellular traps (METs). However, a role for PADs in ET formation in macrophages has not been previously described. Transcripts for PAD2 and PAD4 are found in mature macrophages and these cells can be induced to citrullinate proteins, thus raising the possibility that PADs may play a direct role in ET formation in macrophages via histone hypercitrullination. In breast and visceral white adipose tissue from obese patients, infiltrating macrophages are often seen to surround dead adipocytes forming characteristic “crown-like structures” (CLS) and the presence of these lesions is associated with increased levels of inflammatory mediators. In light of these observations, we have initiated studies to test whether PADs are expressed in CLS macrophages and whether these macrophages might form METs. Our preliminary findings show that PAD2 (and to a lesser extent, PAD4) is expressed in both in the macrophage cell line (RAW 264.7) and in CLS lesions. Additionally, we provide evidence that macrophage-derived extracellular histones are seen around presumptive macrophages within CLS lesions and that these histones contain the H4Cit3 modification. These initial findings support our hypothesis that obesity-induced adipose tissue inflammation promotes the formation of METs within CLS lesions via PAD-mediated histone hypercitrullination. Subsequent studies are underway to further validate these findings and to investigate the role in PAD-mediated MET formation in CLS function in the mammary gland.
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DOI：
10.1084/jem.20100239
发表时间：
2010-08-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Li P;Li M;Lindberg MR;Kennett MJ;Xiong N;Wang Y
通讯作者：
Wang Y
DOI：
10.1083/jcb.200806072
发表时间：
2009-01-26
期刊：
The Journal of cell biology
影响因子：
--
作者：
Wang Y;Li M;Stadler S;Correll S;Li P;Wang D;Hayama R;Leonelli L;Han H;Grigoryev SA;Allis CD;Coonrod SA
通讯作者：
Coonrod SA
影响因子：
6.7
作者：
Urban CF;Ermert D;Schmid M;Abu-Abed U;Goosmann C;Nacken W;Brinkmann V;Jungblut PR;Zychlinsky A
通讯作者：
Zychlinsky A
影响因子：
44.1
作者：
Remijsen, Quinten;Vanden Berghe, Tom;Vandenabeele, Peter
通讯作者：
Vandenabeele, Peter
影响因子：
3
作者：
Mohanan S;Cherrington BD;Horibata S;McElwee JL;Thompson PR;Coonrod SA
通讯作者：
Coonrod SA