Expression of the serine protease inhibitor neuroserpin in cells of the human myeloid lineage
Expression of the serine protease inhibitor neuroserpin in cells of the human myeloid lineage
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DOI：
10.1160/th06-09-0543
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发表时间：
2007-03-01
影响因子：
6.7
通讯作者：
Birch, Nigel P.
中科院分区：
文献类型：
--
作者：
Kennedy, Sarah A.;van Diepen, Angela C.;Birch, Nigel P.
骨髓中的髓样祖细胞分化成免疫系统的大多数主要细胞类型，包括巨噬细胞和树突状细胞。这些细胞在先天免疫和适应性免疫中起着重要作用。它们表达许多蛋白酶和蛋白酶抑制剂，包括丝氨酸蛋白酶抑制剂或丝氨酸蛋白酶抑制剂超家族的成员。在这项研究中，我们报告的差异表达neuroserpin在人类髓系细胞。Neuroserpin在单核细胞分化为巨噬细胞和树突状细胞后高度表达和分泌。用脂多糖激活树突状细胞导致neuroserpin mRNA水平增加，但没有neuroserpin分泌。共聚焦免疫荧光显微镜显示neuroserpin差异定位于人类骨髓细胞。在巨噬细胞和树突状细胞中，它集中在靠近质膜的囊泡中。大多数活化的树突状细胞还表现出与溶酶体/晚期内体标记物LAMP-I共定位的神经丝氨酸蛋白酶抑制剂的细胞内局灶性浓度。由于神经丝氨酸蛋白酶抑制剂抑制组织纤溶酶原激活剂，tPA和纤溶酶原激活剂通道-I（派-1）的表达进行了比较分析。该分析揭示了PAI-1和neuroserpin的差异表达，表明它们在人免疫细胞中可能具有不同的功能。
Myeloid progenitors in the bone marrow differentiate into most of the major cell types of the immune system, including macrophages and dendritic cells. These cells play important roles in both innate and adaptive immunity. They express a number of proteases and protease inhibitors including members of the serine proteinase inhibitor or serpin superfamily. In this study we report the differential expression of neuroserpin in cells of the human myeloid lineage. Neuroserpin was highly expressed and secreted following the differentiation of monocytes to macrophages and dendritic cells. Activation of dendritic cells with lipo-polysaccharide resulted in increased neuroserpin mRNA levels but no neuroserpin secretion. Confocal immunofluorescence microscopy showed neuroserpin was differentially localised in human myeloid cells. In macrophages and dendritic cells it was concentrated in vesicles located in close proximity to the plasma membrane. The majority of activated dendritic cells also exhibited an intracellular focal concentration of neuroserpin which co-localised with the lysosomal/late endosomal marker LAMP-I. As neuroserpin inhibits tissue plasminogen activator, a comparative analysis of tPA and plasminogen activator inhibitor-I (PAI-1) expression was undertaken. This analysis revealed differential expression of PAI-I and neuroserpin suggesting they may have different functions in human immune cells.