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慢性鼻窦炎中PAPP-A模式的表征

Characterization of PAPP-A Patterns in Chronic Rhinosinusitis.

基础研究鼻科IF 5.1Q2

文献信息

中文摘要

目的:
我们团队此前已证实,在伴有鼻息肉的慢性鼻窦炎(CRSwNP)中,pappalysin-A/胰岛素样生长因子结合蛋白/胰岛素样生长因子-1(PAPP-A/IGFBP-4/5/IGF-1轴)呈高水平表达。PAPP-A在炎症性疾病和癌症中发挥关键作用。本研究旨在定位慢性鼻窦炎(CRS)组织、炎症细胞及不同原代细胞中的PAPP-A。
患者与方法:
通过免疫组织化学(IHC)在CRSwNP(n=41)、CRSsNP患者(n=12)以及对照组(n=12)的组织中定位PAPP-A。CRSwNP组织中嗜酸性粒细胞丰度的数据来自常规病理检查。采用ELISA非侵入性地定量CRSwNP黏液(n=67)中的PAPP-A和ECP。在细胞水平上,通过免疫荧光(IF)在来自CRSwNP(n=18)的免疫细胞和原代细胞中定位PAPP-A。
结果:
IHC揭示了CRSwNP中PAPP-A的三种分布模式,且与嗜酸性粒细胞丰度相关。此外,不同免疫细胞的IF证实,除未明确的T细胞亚群外,嗜酸性粒细胞高合成PAPP-A,肥大细胞中等合成。此外,还显示了PAPP-A在上皮细胞和成纤维细胞胞质及细胞膜中的囊泡状分布。最后,ECP和PAPP-A在CRSwNP黏液中显示出显著相关性。
结论:
我们的工作首次阐明了CRSwNP中PAPP-A的三种分布模式。这强调了PAPP-A潜在的炎症作用,尤其是在CRSwNP中。靶向PAPP-A/IGFBP/IGF-1轴可能成为嗜酸性粒细胞丰度高的CRSwNP的一种新治疗方法。

英文摘要

PURPOSE: High-level expression of pappalysin-A/insulin-like growth factor binding protein/insulin-like growth factor-1 (PAPP-A/IGFBP-4/5/IGF-1 axis) in Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) was previously demonstrated by our group. PAPP-A plays a key role in inflammatory diseases and cancer. The aim of this study was to localize PAPP-A in Chronic Rhinosinusitis (CRS), within tissue, inflammatory and different primary cells.
PATIENTS AND METHODS: PAPP-A was localized by immunohistochemistry (IHC) in tissues of CRSwNP (n=41), CRSsNP patients (n=12) as well as in controls (n=12). The data of eosinophil abundance in CRSwNP tissues was obtained from routine pathology. ELISA was used to quantify PAPP-A and ECP non-invasively in CRSwNP mucus (n=67). On a cellular level, PAPP-A was localized by immunofluorescence (IF) in immune and primary cells from CRSwNP (n=18).
RESULTS: IHC revealed three distribution patterns of PAPP-A in CRSwNP correlated to the eosinophil abundance. Moreover, IF of different immune cells confirmed the high PAPP-A synthesis by eosinophils, in addition to unspecified subpopulation of T-cells and moderately in mast cells. Besides, a vesicular distribution of PAPP-A in the cytoplasm and the membrane of epithelial and fibroblast cells was shown. Finally, ECP and PAPP-A proved a significant correlation in CRSwNP mucus.
CONCLUSION: Our work is the first to illustrate the three distribution patterns of PAPP-A in CRSwNP. This underlines the potential inflammatory role of PAPP-A, particularly in CRSwNP. Targeting the PAPP-A/IGFBP/IGF-1-axis may be a new therapeutic approach for CRSwNP with high eosinophil abundance.