Increased expression of the chemokine CCL23 in eosinophilic chronic rhinosinusitis with nasal polyps

被引:84
|
作者
Poposki, Julie A. [1 ]
Uzzaman, Ashraf [1 ]
Nagarkar, Deepti R. [1 ]
Chustz, Regina T. [1 ]
Peters, Anju T. [1 ]
Suh, Lydia A. [1 ]
Carter, Roderick [1 ]
Norton, James [1 ]
Harris, Kathleen E. [1 ]
Grammer, Leslie C. [1 ]
Tan, Bruce K. [2 ]
Chandra, Rakesh K. [2 ]
Conley, David B. [2 ]
Kern, Robert C. [2 ]
Schleimer, Robert P. [2 ]
Kato, Atsushi [1 ]
机构
[1] Northwestern Univ, Feinberg Sch Med, Div Allergy & Immunol, Dept Med, Chicago, IL 60611 USA
[2] Northwestern Univ, Feinberg Sch Med, Dept Otolaryngol, Chicago, IL 60611 USA
基金
美国国家卫生研究院;
关键词
Chronic rhinosinusitis; nasal polyps; CCL23; CCR1; eosinophils; aspirin sensitivity; ENDOTHELIAL GROWTH-FACTOR; CELL-ACTIVATING FACTOR; CC-CHEMOKINE; MATRIX METALLOPROTEINASE-2; INFLAMMATORY MEDIATORS; DENDRITIC CELLS; MESSENGER-RNA; TNF FAMILY; RECEPTOR; MACROPHAGES;
D O I
10.1016/j.jaci.2011.03.017
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: Chronic rhinosinusitis (CRS) is a heterogeneous chronic disease characterized by local inflammation of the sinonasal tissues. The pathogenesis of CRS remains controversial, but it has been associated with the accumulation of various immune and inflammatory cells in sinus tissue. Objectives: The objective of this study was to investigate the expression of the chemokine CCL23, which is known to bind to CCR1 and recruit monocytes, macrophages, and dendritic cells, in patients with CRS. Methods: We collected nasal tissue from patients with CRS and control subjects. We assayed mRNA for CCL23 by using real-time PCR and measured CCL23 protein by means of ELISA, immunohistochemistry, and immunofluorescence. Results: CCL23 mRNA levels were significantly increased in nasal polyps (NPs) from patients with CRS with nasal polyps (CRSwNP; P < .05) compared with inferior turbinate and uncinate tissue from patients with CRS or control subjects. CCL23 protein levels were also increased in NPs, although these levels were not statistically significant. Immunohistochemical analysis revealed CCL23 expression in mucosal epithelial cells and inflammatory cells, but accumulation of CCL23(+) inflammatory cells occurred only in NPs. Immunofluorescence data showed CCL23 colocalization with eosinophil cationic protein-positive eosinophils. The concentration of CCL23 in NPs positively correlated with the concentration of eosinophil cationic protein, suggesting that eosinophils are major CCL23-producing cells in NPs. Finally, we found that CCL23 protein levels were significantly increased in NPs from patients with CRSwNP with aspirin sensitivity. Conclusion: Overproduction of CCL23 in NPs might contribute to the pathogenesis of eosinophilic CRSwNP through the recruitment of CCR1(+) inflammatory cells, including monocytes and macrophages, and the amplification of local inflammation. (J Allergy Clin Immunol 2011; 128: 73-81.)
引用
收藏
页码:73 / U123
页数:13
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