Expression, localization, and regulation of NOS in human mast cell lines: effects on leukotriene production
Expression, localization, and regulation of NOS in human mast cell lines: effects on leukotriene production
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DOI：
10.1182/blood-2003-08-2990
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发表时间：
2004-07-15
期刊：
影响因子：
20.3
通讯作者：
Befus, AD
中科院分区：
文献类型：
--
作者：
Gilchrist, M;McCauley, SD;Befus, AD
一氧化氮（NO）是由一氧化氮合酶（NOS）产生的一种强有力的自由基，在健康和疾病中具有多效性活性。由于肥大细胞（MC）在体内平衡和病理学中起着重要作用，我们研究了NOS表达和NO产生在人类MC人群。内皮型一氧化氮合酶（eNOS）在人MC系和皮肤来源的MC中普遍表达，而神经型一氧化氮合酶（nNOS）在所研究的MC群体中不表达。诱导型（iNOS）亚型在人MC中未检测到。生长因子非依赖性（HMC-1）和依赖性（LAD 2）MC系显示主要的细胞核eNOS蛋白定位，与较弱的胞浆表达。nNOS在HMC-1中显示出排他性的细胞质定位。激活钙离子载体（A23187）或IgE-抗IgE诱导eNOS磷酸化和易位到细胞核和细胞核和细胞质NO的形成。eNOS与MC核中的白三烯（LT）起始酶5-脂氧合酶（5-LO）共定位。NO供体S-亚硝基谷胱甘肽（SNOG）抑制LT释放，而NOS抑制剂N-G-硝基-L-精氨酸甲酯（L-NAME）以剂量依赖方式增强LT释放。因此，人MC系在细胞质和细胞核区室中产生NO，并且内源性产生的NO可以调节MC的LT产生。(C)2004年，美国血液学会。
Nitric oxide (NO) is a potent radical produced by nitric oxide synthase (NOS) and has pleiotrophic activities in health and disease. As mast cells (MCs) play a central role in both homeostasis and pathology, we investigated NOS expression and NO production in human MC populations. Endothelial NOS (eNOS) was ubiquitously expressed in both human MC lines and skin-derived MCs, while neuronal NOS (nNOS) was variably expressed in the MC populations studied. The inducible (iNOS) isoform was not detected in human MCs. Both growth factor-independent (HMC-1) and -dependent (LAD 2) MC lines showed predominant nuclear eNOS protein localization, with weaker cytoplasmic expression. nNOS showed exclusive cytoplasmic localization in HMC-1. Activation with Ca2+ ionophore (A23187) or IgE-anti-IgE induced eNOS phosphorylation and translocation to the nucleus and nuclear and cytoplasmic NO formation. eNOS colocalizes with the leukotriene (LT)-initiating enzyme 5-lipoxygenase (5-LO) in the MC nucleus. The NO donor, S-nitrosoglutathione (SNOG), inhibited, whereas the NOS inhibitor, N-G-nitro-L-arginine methyl ester (L-NAME), potentiated LT release in a dose-dependent manner. Thus, human MC lines produce NO in both cytoplasmic and nuclear compartments, and endogenously produced NO can regulate LT production by MCs. (C) 2004 by The American Society of Hematology.