- 作者：Koen Van Crombruggen ; PhD ; koen.vancrombruggen@ugent.be ; Gabriele Holtappels ; Natalie De Ruyck ; Lara Derycke ; PhD ; Peter Tomassen ; MD ; Claus Bachert ; MD ; PhD
- 关键词：Receptor for advanced glycation end products ; eosinophil cationic protein ; Staphylococcus aureus ; airway inflammation
- 刊名：Journal of Allergy and Clinical Immunology
- 出版年：2012
- 期刊代码：158_00916749
- 类别：med
- 出版时间：June, 2012
- 卷：129
- 期：6
- 页码：1515-1521.e8
- 文件大小：612 K
Background
The receptor for advanced glycation end products (RAGE) is a multiligand receptor that exists as a membrane-bound (mRAGE) form and a soluble (sRAGE) form. RAGE is reported to play a role in diverse pathologies including lower airway conditions, but the exact mechanism of action remains poorly understood. In the upper airways, the involvement of RAGE remains completely unexplored.Objective
To investigate the involvement of RAGE in the human upper airway conditions chronic rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis with nasal polyps (CRSwNP).
Methods
Protein levels of sRAGE, mRAGE, IL-5, and eosinophil cationic protein (ECP) were quantitatively assessed in inflamed tissue of CRSsNP and CRSwNP patients. Nasal tissue of subjects without disease served as control. Ex聽vivo human sinonasal tissue stimulation assays were used to assess the effect of Staphylococcus aureus and ECP on sRAGE processing.
Results
sRAGE protein levels were higher in CRSsNP tissue, whereas mRAGE protein levels were lower than in controls. In CRSwNP patients, both tissue sRAGE and mRAGE protein levels were reduced. Low tissue sRAGE protein concentrations were associated with high IL-5 and ECP protein levels. In聽vitro, S aureus induced the release of sRAGE from the tissue, while ECP was shown to be implicated in the breakdown of free sRAGE.
Conclusions
We demonstrate for the first time that RAGE protein is highly expressed in human upper airways under normal physiology and that it is subject to differential processing in CRSsNP and CRSwNP, identifying S aureus and ECP as novel and crucial players in this process.