Do tissue levels of autoantigenic aminoacyl-tRNA synthetase predict clinical disease?
Do tissue levels of autoantigenic aminoacyl-tRNA synthetase predict clinical disease?
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DOI：
10.1016/j.mehy.2005.06.016
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发表时间：
2005-01-01
影响因子：
4.7
通讯作者：
Scaffidi, LE
中科院分区：
文献类型：
--
作者：
Kron, MA;Petridis, M;Scaffidi, LE
大多数自身免疫性疾病的病因尚不完全清楚。氨基酰基trna合成酶（AARS）是一个负责蛋白质合成的异质酶家族，其次要功能包括在自身免疫性肌炎中的作用。一部分特发性炎性肌病患者表现出针对特定细胞质AARS的自身抗体，并且人天冬酰胺- trna合成酶（AsnRS）已被证明是一种与CCR3趋化因子受体相互作用的有效趋化因子。趋化细胞质酶可能导致组织炎症的一种方式是，如果它在特定的受伤组织中大量存在，从而在细胞损伤时释放到微环境中。为了验证这一假设，我们研究了6个人体组织中AsnRS mRNA的相对水平。1.6 kbF RNA探针在人体肺、脑、心脏、骨骼肌、胰腺和肝脏的Northern blot分析中发现了高度可变的相应mRNA水平。肌肉和胰腺的信号水平最高。抗重组人AsnRS的多克隆抗体在胰腺，特别是胰岛细胞中发现了丰富的抗原物质。因此，内源性促炎自身抗原的局部丰度可能为组织特异性免疫介导病理的延续或恶化提供了一种解释。(c) 2005 Elsevier Ltd版权所有。
The etiologies of most autoimmune diseases are not completely understood. Aminoacyl-tRNA synthetases (AARS) are a family of heterogenous enzymes responsible for protein synthesis and whose secondary functions include a rote in autoimmune myositis. A subset of patients with idiopathic inflammatory myopathies demonstrate autoantibody against specific cytoplasmic AARS and the human asparaginyl-tRNA synthetase (AsnRS) has been shown to be a potent chemokine that interacts with CCR3 chemokine receptors. One way in which a chemotactic cytoplasmic enzyme might contribute to tissue inflammation is if it were abundant in a specific injured tissue and thereby released to the microenvironment at times of cellular damage. To test this hypothesis, the relative levels of AsnRS mRNA were studied in six human tissues. A 1.6 kbF RNA probe identified highly variable levels of the corresponding mRNA in Northern blot analysis of human lung, brain, heart, skeletal muscle, pancreas and Liver. The highest levels of signal were noted in muscle and pancreas. Polyclonal antibody raised against recombinant human AsnRS identified abundant antigenic material in the pancreas, in particular in islet cells. Thus, the local abundance of an endogenous pro-inflammatory autoantigen may provide one explanation for perpetuation or exacerbation of tissue specific immune-mediated pathologies. (c) 2005 Elsevier Ltd. All rights reserved.