Expression of antizyme inhibitor 2 in mast cells and role of polyamines as selective regulators of serotonin secretion.
Expression of antizyme inhibitor 2 in mast cells and role of polyamines as selective regulators of serotonin secretion.
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DOI：
10.1371/journal.pone.0006858
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发表时间：
2009-08-31
期刊：
影响因子：
3.7
通讯作者：
Andersson LC
中科院分区：
文献类型：
--
作者：
Kanerva K;Lappalainen J;Mäkitie LT;Virolainen S;Kovanen PT;Andersson LC
在IgE介导的活化下，肥大细胞（MC）胞质分泌颗粒外排并释放多种生物活性物质，引发炎症反应。多胺介导许多细胞和生理功能。我们在这里报告，MCs表达抗酶抑制剂2（AZIN 2），多胺生物合成的激活剂，以前报道只在大脑和睾丸中表达。我们研究了AZIN 2在静息和活化MC中的细胞内定位。此外，我们还研究了多胺的功能作用，下游效应的AZIN 2，作为潜在的调节MC活动。免疫染色显示AZIN 2在原发性和肿瘤性人类和啮齿动物MC中表达。我们证明，AZIN 2定位于Vamp-8阳性，含降钙素的MC颗粒的子集，但不含类胰蛋白酶的颗粒，如双重免疫荧光染色所示。此外，MCs的激活诱导AZIN 2表达及其再分布的快速上调，表明AZIN 2在分泌颗粒胞吐中的作用。我们还证明，从激活的MCs的5-羟色胺的释放是多胺依赖性的，而释放组胺和β-氨基己糖苷酶不是，表明颗粒亚型特异性功能的多胺。该研究首次报道了AZIN 2在脑和睾丸外的表达，并证明了MCs中内源性AZIN 2的细胞内定位。颗粒亚型特异性表达和MC激活后的诱导表明AZIN 2作为多胺生物合成的局部原位调节剂与含麦考诺宁的MC颗粒相关的作用。此外，我们的数据表明，多胺作为选择性调节剂的5-羟色胺从MC释放的新功能。
Upon IgE-mediated activation, mast cells (MC) exocytose their cytoplasmic secretory granules and release a variety of bioactive substances that trigger inflammatory responses. Polyamines mediate numerous cellular and physiological functions. We report here that MCs express antizyme inhibitor 2 (AZIN2), an activator of polyamine biosynthesis, previously reported to be exclusively expressed in the brain and testis. We have investigated the intracellular localization of AZIN2 both in resting and activated MCs. In addition, we have examined the functional role of polyamines, downstream effectors of AZIN2, as potential regulators of MC activity. Immunostainings show that AZIN2 is expressed in primary and neoplastic human and rodent MCs. We demonstrate that AZIN2 localizes in the Vamp-8 positive, serotonin-containing subset of MC granules, but not in tryptase-containing granules, as revealed by double immunofluorescence stainings. Furthermore, activation of MCs induces rapid upregulation of AZIN2 expression and its redistribution, suggesting a role for AZIN2 in secretory granule exocytosis. We also demonstrate that release of serotonin from activated MCs is polyamine-dependent whereas release of histamine and β-hexosaminidase is not, indicating a granule subtype-specific function for polyamines. The study reports for the first time the expression of AZIN2 outside the brain and testis, and demonstrates the intracellular localization of endogenous AZIN2 in MCs. The granule subtype-specific expression and its induction after MC activation suggest a role for AZIN2 as a local, in situ regulator of polyamine biosynthesis in association with serotonin-containing granules of MCs. Furthermore, our data indicates a novel function for polyamines as selective regulators of serotonin release from MCs.
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影响因子：
4.1
作者：
BUEB, JL;DASILVA, A;LANDRY, Y
通讯作者：
LANDRY, Y
DOI：
10.1073/pnas.070055897
发表时间：
2000-04-25
影响因子：
11.1
作者：
Ivanov, IP;Rohrwasser, A;Atkins, JF
通讯作者：
Atkins, JF
影响因子：
6.1
作者：
Lappalainen, J.;Lindstedt, K. A.;Kovanen, P. T.
通讯作者：
Kovanen, P. T.
影响因子：
4.1
作者：
MCCORMACK, JG
通讯作者：
MCCORMACK, JG
影响因子：
56.9
作者：
FICKER, E;TAGLIALATELA, M;BROWN, AM
通讯作者：
BROWN, AM