Vesicular monoamine transporter 2 (VMAT2) expression in hematopoietic cells and in patients with systemic mastocytosis

Vesicular monoamine transporter 2 (VMAT2) expression in hematopoietic cells and in patients with systemic mastocytosis
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DOI:
10.1369/jhc.5a6739.2005
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发表时间:
2006-02-01
影响因子:
3.2
通讯作者:
Weihe, E
Weihe, E
中科院分区:
生物学3区
文献类型:
--
作者:
Anlauf, M;Schäfer, MKH;Weihe, E

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单胺被摄取到分泌颗粒中是由囊泡单胺转运蛋白VMAT 1和VMAT 2介导的。在这项研究中,我们分析了他们的表达在炎症和造血细胞和患者患有系统性肥大细胞增多症(SM)和慢性粒细胞白血病(CIVIL)。应用免疫组织化学、放射性原位杂交、真实的时间RT-PCR、双荧光共聚焦激光扫描显微镜和免疫电镜等方法对正常人和猴组织标本以及SM和CIVIL患者组织进行分析。在正常组织标本中,VMAT 2,但不是VMAT 1,表达在肥大细胞,巨核细胞,血小板,嗜碱性粒细胞,和皮肤朗格汉斯细胞。进一步的造血和淋巴细胞显示VMAT不表达。VMAT 2在所有类型的SM中表达,如与肥大细胞标记物类胰蛋白酶共表达所示。在CIVIL中,VMAT 2表达保留在肿瘤性巨核细胞和嗜碱性粒细胞中。总之,VMAT 2在肥大细胞,巨核细胞,血小板,嗜碱性粒细胞和皮肤朗格汉斯细胞中的鉴定提供了证据,这些细胞具有单胺储存和处理的分子机制。VMAT 2识别正常和肿瘤性肥大细胞、巨核细胞和嗜碱性粒细胞,因此可能成为诊断肥大细胞增多症和涉及巨核细胞和嗜碱性粒细胞的恶性系统性疾病的有价值的工具。
Uptake of monoamines into secretory granules is mediated by the vesicular monoamine transporters VMAT1 and VMAT2. In this study, we analyzed their expression in inflammatory and hematopoietic cells and in patients suffering from systemic mastocytosis (SM) and chronic myelogenous leukemia (CIVIL). Normal human and monkey tissue specimens and tissues from patients suffering from SM and CIVIL were analyzed by means of immunohistochemistry, radioactive in situ hybridization, real time RT-PCR, double fluorescence confocal laser scanning microscopy, and immunoelectron microscopy. In normal tissue specimens, VMAT2, but not VMAT1, was expressed in mast cells, megakaryocytes, thrombocytes, basophil granulocytes, and cutaneous Langerhans cells. Further hematopoietic and lymphoid cells showed no expression of VMATs. VMAT2 was expressed in all types of SM, as indicated by coexpression with the mast cell marker tryptase. In CIVIL, VMAT2 expression was retained in neoplastic megakaryocytes and basophil granulocytes. In conclusion, the identification of VMAT2 in mast cells, megakaryocytes, thrombocytes, basophil granulocytes, and cutaneous Langerhans cells provides evidence that these cells possess molecular mechanisms for monoamine storage and handling. VMAT2 identifies normal and neoplastic mast cells, megakaryocytes, and basophil granulocytes and may therefore become a valuable tool for the diagnosis of mastocytosis and malignant systemic diseases involving megakaryocytes and basophil granulocytes.