Expression, regulation and functional activities of aminopeptidase N (EC 3.4.11.2; APN; CD13) on murine macrophage J774 cell line
Expression, regulation and functional activities of aminopeptidase N (EC 3.4.11.2; APN; CD13) on murine macrophage J774 cell line
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DOI：
10.1016/j.imbio.2010.06.005
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发表时间：
2011-01-01
期刊：
影响因子：
2.8
通讯作者：
Majhen, Dragomira
中科院分区：
文献类型：
--
作者：
Gabrilovac, Jelka;Cupic, Barbara;Majhen, Dragomira
氨肽酶N （APN; CD13）是一种普遍存在的膜结合酶。在造血细胞上表达的APN通过调节局部趋化肽的浓度和微调抗原呈递参与炎症和免疫反应。本研究的数据首次表明，经常被用作模型细胞系的小鼠巨噬细胞系J774细胞在转录水平和膜蛋白水平上均表达CD13，并具有氨基肽酶N （APN）活性。CD13/APN在J774细胞上的转录表达水平与参与免疫应答的正常细胞的转录表达水平进行了比较。CD13/APN mRNA在腹腔巨噬细胞中表达水平最高，其次是J774细胞和脾细胞，而淋巴结、胸腺和骨髓细胞CD13/APN mRNA表达水平较低。此外，促炎ifn - γ可上调J774细胞的CD13 (mRNA、蛋白和APN)，这与已知的CD13/APN在炎症反应中的作用一致。CD13与MHC-II和CD86的共调节与报道的APN在抗原呈递中的作用一致。J774细胞上的CD13与甘露糖受体（MR）共定位，并通过卵清蛋白在MR连接后共内化，提示CD13在MR介导的吞噬作用中具有新的功能。CD13的功能不依赖于APN酶的活性。抗炎药物地塞米松降低ifn - γ诱导的CD13升高。地塞米松对J774细胞CD13的下调可能与抗炎药物作用于正常巨噬细胞的机制有关。(C) 2010 Elsevier GmbH版权所有。
Aminopeptidase N (APN; CD13) is a ubiquitous membrane-bound enzyme. Expressed on haematopoietic cells APN participates in inflammatory and immune responses by regulating local concentration of chemotactic peptides and by fine-tuning antigen presentation. The data of this study have shown for the first time that cells of murine macrophage line, J774, often used as a model cell line, express CD13 both at transcriptional level and at the level of membrane protein with aminopeptidase N (APN) activity. The level of transcriptional expression of CD13/APN on J774 cells was compared to that found on normal cells participating in immune responses. The highest CD13/APN level was found in peritoneal macrophages, followed by J774 cells and splenocytes, whereas lymph node, thymus and bone-marrow cells expressed low level of CD13/APN mRNA. Further, the CD13 (mRNA, protein and APN) on J774 cells could be up-regulated by pro-inflammatory IFN-gamma which is in agreement with the known role of CD13/APN in inflammatory responses. Co-regulation of CD13 with MHC-II and CD86 is in line with the reported role of APN expressed on human cells in antigen presentation. CD13 on J774 cells co-localize with mannose receptors (MR), and co-internalize upon MR ligation by ovalbumin, suggesting a new function of CD13 in MR-mediated phagocytosis. That function of CD13 is independent of APN enzyme activity. Anti-inflammatory drug dexamethasone diminished the IFN-gamma-induced increase of CD13. The observed down-regulation of CD13 on J774 cells by dexamethasone might be relevant as a possible mechanism involved in action of anti-inflammatory drugs on normal macrophages. (C) 2010 Elsevier GmbH. All rights reserved.