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生长相关癌基因α和粒细胞趋化蛋白-2作为慢性鼻窦炎中嗜中性粒细胞趋化因子的主要作用。

Primary role of growth-related oncogene-alpha and granulocyte chemotactic protein-2 as neutrophil chemoattractants in chronic rhinosinusitis.

作者信息

Rudack C, Sachse F, Alberty J

机构信息

Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Münster, Münster, Germany.

出版信息

Clin Exp Allergy. 2006 Jun;36(6):748-59. doi: 10.1111/j.1365-2222.2006.02501.x.

DOI:10.1111/j.1365-2222.2006.02501.x
PMID:16776676
Abstract

BACKGROUND

The aetiology of chronic rhinosinusitis (CRS) remains unclear. The purpose of this study was to investigate neutrophil-attracting chemokine patterns in CRS without nasal polyposis.

METHODS

The biological activity of the chemokines was identified using a two-step high-performance liquid chromatography (HPLC) technique combined with a bioassay in extracts from 55 CRS patients, and in the turbinate mucosa (TM) of patients (N=51) undergoing septumplasty. The biologic activity of each chemokine was assessed using blocking antibodies to chemokines. Immunolocalization of detected neutrophil chemokines was performed by quantitative evaluation of immunohistochemistry. Besides, PCR analysis was performed to quantify neutrophil chemokine mRNA.

RESULTS

In CRS, the chemokines primarily detected by two-step HPLC were growth-related oncogene-alpha (GRO-alpha) and the granulocyte chemotactic protein-2 (GCP-2). Blocking of GCP-2 and GRO-alphad each resulted in chemotaxis inhibition rates of 43.3% and 35.9%, respectively, whereas anti-IL-8 and anti-ENA-78 had no effect. Both GCP-2 and GRO-alphad were generally synthesized by the surface epithelium and mucosal glands while GRO-alpha in particular was synthesized by endothelial cells, as shown by immunohistochemistry. The concentrations of the chemokines IL-8 and epithelial cell-derived neutrophil attractant-78 (ENA-78) were low in CRS and TM.

CONCLUSION

It appears that both GRO-alpha and GCP-2 contribute to neutrophil chemotaxis in CRS, whereas IL-8 and ENA-78 appear to be of secondary importance for the chemotaxis of neutrophils in this condition. The expression of chemokines in mucosal gland cells is the main phenomenon involved in constitutive neutrophil chemotaxis in the TM.

摘要

背景

慢性鼻-鼻窦炎(CRS)的病因仍不明确。本研究旨在调查无鼻息肉的CRS患者中嗜中性粒细胞趋化因子模式。

方法

采用两步高效液相色谱(HPLC)技术结合生物测定法,对55例CRS患者的提取物以及51例接受鼻中隔成形术患者的鼻甲黏膜(TM)中趋化因子的生物活性进行鉴定。使用趋化因子阻断抗体评估每种趋化因子的生物活性。通过免疫组织化学定量评估对检测到的嗜中性粒细胞趋化因子进行免疫定位。此外,进行PCR分析以定量嗜中性粒细胞趋化因子mRNA。

结果

在CRS中,通过两步HPLC主要检测到的趋化因子是生长相关癌基因-α(GRO-α)和粒细胞趋化蛋白-2(GCP-2)。阻断GCP-2和GRO-α分别导致趋化抑制率为43.3%和35.9%,而抗白细胞介素-8(IL-8)和抗嗜酸性粒细胞趋化蛋白-78(ENA-78)则无作用。免疫组织化学显示,GCP-2和GRO-α通常由表面上皮和黏膜腺合成,特别是GRO-α由内皮细胞合成。CRS和TM中趋化因子IL-8和上皮细胞衍生的嗜中性粒细胞趋化因子-78(ENA-78)的浓度较低。

结论

似乎GRO-α和GCP-2均有助于CRS中嗜中性粒细胞趋化,而IL-8和ENA-78在这种情况下对嗜中性粒细胞趋化似乎次要。黏膜腺细胞中趋化因子的表达是TM中组成性嗜中性粒细胞趋化的主要现象。

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