Increased expression of CC chemokine ligand 18 in patients with chronic rhinosinusitis with nasal polyps.
Increased expression of CC chemokine ligand 18 in patients with chronic rhinosinusitis with nasal polyps.
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DOI：
10.1016/j.jaci.2011.08.021
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发表时间：
2012-01
期刊：
影响因子：
--
通讯作者：
Kato A
中科院分区：
文献类型：
--
作者：
Peterson S;Poposki JA;Nagarkar DR;Chustz RT;Peters AT;Suh LA;Carter R;Norton J;Harris KE;Grammer LC;Tan BK;Chandra RK;Conley DB;Kern RC;Schleimer RP;Kato A
与非息肉样鼻窦炎 (CRSsNP) 不同，慢性鼻窦炎伴鼻息肉 (CRSwNP) 与 Th2 主导型炎症（包括嗜酸性粒细胞增多）相关。已知趋化因子 CCL18/PARC（肺和激活调节趋化因子）可招募幼稚 T 细胞、B 细胞和未成熟树突状细胞，并激活成纤维细胞。 CCL18被认为与Th2相关的炎症性疾病有关，包括哮喘和特应性皮炎。本研究的目的是探讨 CCL18 在 CRS 患者中的表达。使用来自对照和 CRS 患者的鼻息肉组织 (NP) 和钩状组织 (UT)，我们通过实时 PCR 检测 CCL18 mRNA 的表达，并通过 ELISA、蛋白质印迹和免疫荧光检测 CCL18 蛋白。与对照受试者的UT组织相比，CCL18 mRNA在CRSwNP患者的NP（p<0.001）和UT（p<0.05）中显着增加，但在CRSsNP患者的UT中没有显着增加。同样，CCL18 蛋白在 CRSwNP 中的 NP 和 UT 中升高，并且在 Samter 三联征患者中水平甚至更高。免疫组织化学分析显示，NP 中炎症细胞中的 CCL18 表达和 CCL18+ 细胞显着增加。免疫荧光数据显示 CCL18 在 NP 中 CD68+/CD163+/巨噬细胞甘露糖受体+M2 巨噬细胞和类胰蛋白酶+肥大细胞中共定位。 CCL18 水平与 M2 巨噬细胞标记相关，但与类胰蛋白酶无关，表明 M2 巨噬细胞是 NP 中主要产生 CCL18 的细胞。 CCL18 的过量产生可能通过其已知的活性促进 CRSwNP 的发病机制，其中包括淋巴细胞和树突状细胞的募集、成纤维细胞的激活以及局部炎症的引发。
Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with Th2-dominant inflammation including eosinophilia, in contrast to non-polypoid CRS (CRSsNP). Chemokine CCL18/PARC (pulmonary and activation regulated chemokine) is known to recruit naïve T cells, B cells, and immature dendritic cells, as well as activate fibroblasts. CCL18is thought to be involved in Th2-related inflammatory diseases including asthma and atopic dermatitis. The objective of this study was to investigate the expression of CCL18 in patients with CRS. Using nasal polyp tissue (NP) and uncinate tissue (UT) from controls and patients with CRS, we examined the expression of CCL18 mRNA by real-time PCR and measured CCL18 protein by ELISA, western blot and immunofluorescence. Compared to UT tissue in control subjects, CCL18 mRNA was significantly increased in NP (p<0.001) and UT (p<0.05) from patients with CRSwNP but not in UT from patients with CRSsNP. Similarly, CCL18 protein was elevated in NP and UT from CRSwNP and levels were even higher in Samter’s triad patients. Immunohistochemical analysis revealed CCL18 expression in inflammatory cells and CCL18+ cells were significantly increased in NP. Immunofluorescence data showed co-localization of CCL18 in CD68+/CD163+/macrophage mannose receptor+ M2 macrophages and tryptase+ mast cells in NP. Levels of CCL18 correlated with markers of M2 macrophages but not with tryptase, suggesting that M2 macrophages are a major CCL18-producing cells in NP. Overproduction of CCL18 might contribute to the pathogenesis of CRSwNP through its known activities, which include recruitment of lymphocytes and dendritic cells, activation of fibroblasts, and initiation of local inflammation.
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DOI：
10.1165/rcmb.2003-0078oc
发表时间：
2003-12-01
影响因子：
6.4
作者：
Atamas, SP;Luzina, IG;White, B
通讯作者：
White, B
影响因子：
4.4
作者：
Martinez, Fernando O.;Gordon, Siamon;Mantovani, Alberto
通讯作者：
Mantovani, Alberto
影响因子：
14.2
作者：
Nomura, L;Gao, B;Leung, DYM
通讯作者：
Leung, DYM
影响因子：
14.2
作者：
Dykewicz, Mark S.;Hamilos, Daniel L.
通讯作者：
Hamilos, Daniel L.
影响因子：
4.4
作者：
Guan, P;Burghes, AHM;McColl, SR
通讯作者：
McColl, SR