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慢性鼻-鼻窦炎中替代激活的巨噬细胞和金黄色葡萄球菌吞噬作用受损。

Alternatively activated macrophages and impaired phagocytosis of S. aureus in chronic rhinosinusitis.

机构信息

The Upper Airway Research Laboratory, Department of Oto-Rhino-Laryngology, Ghent University Hospital, Ghent, Belgium.

出版信息

Allergy. 2011 Mar;66(3):396-403. doi: 10.1111/j.1398-9995.2010.02498.x. Epub 2010 Oct 25.

DOI:10.1111/j.1398-9995.2010.02498.x
PMID:20973804
Abstract

BACKGROUND

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by biased Th2 inflammation and CRS without nasal polyps (CRSsNP) by a Th1 immune response. Colonization by Staphylococcus aureus is increased in CRSwNP. We aimed to determine macrophage phenotypes in nasal mucosa of CRSwNP and CRSsNP and to examine phagocytosis of S. aureus in these pathologies.

METHODS

Macrophage phenotyping was performed by immunohistochemical staining on nasal mucosa sections from 28 patients; in addition flow cytometry analysis was performed. Tissue homogenate protein levels of IFN-γ, IL-5, IL-6, IL-1β, TGF-β, eosinophil cationic protein (ECP) and total IgE were analyzed and correlated with macrophage subtypes. Phagocytosis of S. aureus was analyzed by flow cytometry. Survival of S. aureus in Thp1 cells in the presence of polarizing cytokines was studied in vitro.

RESULTS

By immunohistochemical analysis more M2 macrophages were present in CRSwNP than in CRSsNP. This also was positively correlated with increased levels of IL-5, ECP and locally produced IgE and decreased levels of IL-6, IL-1β and IFN-γ. FACS analysis of dissociated nasal tissue confirmed the presence of increased numbers of M2 macrophages (CD206(+) HLADR(+) CD14(+) CD11c(+) CD20(-) ) in CRSwNP as compared to controls, while the number of M1 macrophages (CD206(-) HLADR(+) CD14(+) CD11c(int) CD16(-) CD20(-) ) was not different. Phagocytosis of S. aureus by human tissue derived macrophages was reduced in CRSwNP as compared to macrophages from the control inferior turbinates.

CONCLUSIONS

Decreased phagocytosis of S. aureus and an M2 activation phenotype in CRSwNP could potentially contribute to persistence of chronic inflammation in CRSwNP.

摘要

背景

慢性鼻-鼻窦炎伴鼻息肉(CRSwNP)的特征是 Th2 炎症偏倚,而不伴鼻息肉的慢性鼻-鼻窦炎(CRSsNP)则表现为 Th1 免疫反应。金黄色葡萄球菌在 CRSwNP 中定植增加。我们旨在确定 CRSwNP 和 CRSsNP 鼻黏膜中的巨噬细胞表型,并研究这些病变中金黄色葡萄球菌的吞噬作用。

方法

对 28 例患者的鼻黏膜切片进行巨噬细胞表型免疫组织化学染色;此外还进行了流式细胞术分析。分析组织匀浆蛋白水平的 IFN-γ、IL-5、IL-6、IL-1β、TGF-β、嗜酸性粒细胞阳离子蛋白(ECP)和总 IgE,并与巨噬细胞亚型相关。通过流式细胞术分析金黄色葡萄球菌的吞噬作用。在存在极化细胞因子的情况下,研究 Thp1 细胞中金黄色葡萄球菌的存活情况。

结果

通过免疫组织化学分析,CRSwNP 中存在更多的 M2 巨噬细胞,明显多于 CRSsNP。这与 IL-5、ECP 和局部产生的 IgE 水平升高以及 IL-6、IL-1β 和 IFN-γ 水平降低呈正相关。对分离的鼻组织进行流式细胞术分析,证实与对照相比,CRSwNP 中存在更多数量的 M2 巨噬细胞(CD206(+)HLADR(+)CD14(+)CD11c(+)CD20(-)),而 M1 巨噬细胞(CD206(-)HLADR(+)CD14(+)CD11c(int)CD16(-)CD20(-))数量无差异。与来自对照下鼻甲的巨噬细胞相比,CRSwNP 中的金黄色葡萄球菌吞噬作用减少。

结论

CRSwNP 中金黄色葡萄球菌吞噬作用降低和 M2 激活表型可能导致 CRSwNP 慢性炎症持续存在。

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