Dormant 5-lipoxygenase in inflammatory macrophages is triggered by exogenous arachidonic acid.
Dormant 5-lipoxygenase in inflammatory macrophages is triggered by exogenous arachidonic acid.
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DOI：
10.1038/s41598-017-11496-3
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发表时间：
2017-09-08
影响因子：
4.6
通讯作者：
Faccioli LH
中科院分区：
文献类型：
--
作者：
Sorgi CA;Zarini S;Martin SA;Sanchez RL;Scandiuzzi RF;Gijón MA;Guijas C;Flamand N;Murphy RC;Faccioli LH
驻留组织巨噬细胞与胚胎前体的分化以及炎症巨噬细胞与骨髓细胞的分化导致巨噬细胞异质性。进一步的可塑性通过它们在细胞培养微环境中极化为 M1 和 M2 亚型的能力而表现出来。然而，类二十烷酸产生的详细调节及其与巨噬细胞生物学的关系仍不清楚。使用脂质组学方法，我们证明骨髓源性（BMDM）和腹膜巨噬细胞之间的类二十烷酸生成谱存在显着差异。在极化的 BMDM 中，除了溶血磷脂酰基转移酶活性外，M1 和 M2 表型还可以通过血栓素 B2、前列腺素 (PG) E2 和 PGD2 产生来区分。尽管在 BMDM 中观察到 Alox5 表达和 5-脂氧合酶 (5-LO) 蛋白的存在，但白三烯产生的缺失反映了 5-LO 活性的受损，这可能是通过添加外源花生四烯酸 (AA) 引发的。 BMDM 5-LO 调节机制对 PGE2/cAMP 通路调节没有反应；然而，降低谷胱甘肽过氧化物酶活性的治疗会增加 AA 刺激后 5-LO 代谢产物的产生。了解类二十烷酸途径与巨噬细胞生物学之间的关系可能为巨噬细胞相关疾病的治疗提供新策略。
The differentiation of resident tissue macrophages from embryonic precursors and that of inflammatory macrophages from bone marrow cells leads to macrophage heterogeneity. Further plasticity is displayed through their ability to be polarized as subtypes M1 and M2 in a cell culture microenvironment. However, the detailed regulation of eicosanoid production and its involvement in macrophage biology remains unclear. Using a lipidomics approach, we demonstrated that eicosanoid production profiles between bone marrow-derived (BMDM) and peritoneal macrophages differed drastically. In polarized BMDMs, M1 and M2 phenotypes were distinguished by thromboxane B2, prostaglandin (PG) E2, and PGD2 production, in addition to lysophospholipid acyltransferase activity. Although Alox5 expression and the presence of 5-lipoxygenase (5-LO) protein in BMDMs was observed, the absence of leukotrienes production reflected an impairment in 5-LO activity, which could be triggered by addition of exogenous arachidonic acid (AA). The BMDM 5-LO regulatory mechanism was not responsive to PGE2/cAMP pathway modulation; however, treatment to reduce glutathione peroxidase activity increased 5-LO metabolite production after AA stimulation. Understanding the relationship between the eicosanoids pathway and macrophage biology may offer novel strategies for macrophage-associated disease therapy.
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影响因子：
4.8
作者：
Evans, JH;Spencer, DM;Leslie, CC
通讯作者：
Leslie, CC
影响因子：
3.6
作者：
Flamand, N;Surette, ME;Borgeat, P
通讯作者：
Borgeat, P
影响因子：
3.4
作者：
Gupta, Shakti;Maurya, Mano Ram;Subramaniam, Shankar
通讯作者：
Subramaniam, Shankar
DOI：
10.1111/j.1432-1033.1995.tb20778.x
发表时间：
1995-08-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
JAKOBSSON, PJ;SHASKIN, P;CLAESSON, HE
通讯作者：
CLAESSON, HE
影响因子：
7.3
作者：
Cassado Ados A;D'Império Lima MR;Bortoluci KR
通讯作者：
Bortoluci KR