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人类肥大细胞中的血清素及其 5-HT1 受体。

Serotonin and its 5-HT1 receptor in human mastocytosis.

机构信息

Dermatology and Venereology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Solna, Stockholm, Sweden.

出版信息

Immunopharmacol Immunotoxicol. 2012 Aug;34(4):679-85. doi: 10.3109/08923973.2011.651222. Epub 2012 Feb 1.

DOI:10.3109/08923973.2011.651222
PMID:22268664
Abstract

CONTEXT

Human mastocytosis is a rare disease, in which the serotonergic system may be involved.

OBJECTIVE

The objective of the present study was to examine the possible presence of serotonin (5-HT) and its 5-HT1A receptor (R) in the skin of patients with mastocytosis. In addition, the effect of the 5-HT1AR was tested on human mastocytosis cells, cultured in vitro.

MATERIALS AND METHODS

The expression of 5-HT and 5-HT1AR in patients with urticaria pigmentosa and mastocytoma was studied using immunohistochemistry. The effects of 8-OH-DPAT, an agonist of 5-HT1AR, on the proliferation (cell number), viability, apoptosis, spontaneous release of histamine, as well as a possible 5-HT metabolism, in the human HMC-1 mast cell line, were investigated.

RESULTS

Both 5-HT and 5-HT1AR were expressed in the mast cells in biopsies of mastocytoma and urticaria pigmentosa, as well as in HMC-1 cells. However, no metabolism of 5-HT by the cell line could be detected by the methodology used. The 5-HT1AR agonist had no significant effect on the viability and number of HMC-1 cells, and was without effect on the apoptosis. At concentrations of 10⁻⁶ mol/L and 10⁻⁸-10⁻¹⁰ mol/L (i.e. also at physiological concentrations), the agonist inhibited histamine release by these cells by as much as 30%.

CONCLUSION

These findings indicate that 5-HT and its 5-HT1AR are expressed in human mastocytosis and that an agonist of the 5-HT1AR might be of value in the treatment of these patients.

摘要

背景

人类肥大细胞增多症是一种罕见的疾病,其中可能涉及 5-羟色胺能系统。

目的

本研究的目的是研究肥大细胞增多症患者皮肤中是否存在血清素(5-HT)及其 5-HT1A 受体(R)。此外,还测试了 5-HT1AR 对体外培养的人类肥大细胞增多症细胞的作用。

材料和方法

使用免疫组织化学研究了荨麻疹性血管性肥大细胞瘤和肥大细胞瘤患者中 5-HT 和 5-HT1AR 的表达。研究了 5-HT1AR 激动剂 8-OH-DPAT 对人 HMC-1 肥大细胞系增殖(细胞数量)、活力、凋亡、组胺自发释放以及可能的 5-HT 代谢的影响。

结果

肥大细胞瘤和荨麻疹性血管性肥大细胞瘤活检中的肥大细胞以及 HMC-1 细胞中均表达 5-HT 和 5-HT1AR。然而,所使用的方法学未能检测到细胞系中 5-HT 的代谢。5-HT1AR 激动剂对 HMC-1 细胞的活力和数量没有显著影响,对凋亡也没有影响。在 10⁻⁶mol/L 和 10⁻⁸-10⁻¹⁰mol/L 的浓度下(即生理浓度下),激动剂抑制这些细胞的组胺释放多达 30%。

结论

这些发现表明 5-HT 和其 5-HT1AR 在人类肥大细胞增多症中表达,5-HT1AR 的激动剂可能对这些患者的治疗有价值。

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