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RAGE processing in chronic airway conditions: involvement of Staphylococcus aureus and ECP

Koen Van Crombruggen UGent, Gabriële Holtappels UGent, Natalie De Ruyck UGent, Lara Derycke UGent, PETER TOMASSEN UGent and Claus Bachert UGent (2012) JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. 129(6). p.1515-1521
abstract
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 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 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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
RECOGNITION RECEPTOR RAGE, SOLUBLE RECEPTOR, IDIOPATHIC PULMONARY-FIBROSIS, GLYCATION END-PRODUCTS, airway inflammation, Staphylococcus aureus, Receptor for advanced glycation end products, eosinophil cationic protein, LUNG INJURY, NASAL POLYPOSIS, BETA-TOXIN, DIFFERENTIATION, EXPRESSION, SRAGE
journal title
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
J. Allergy Clin. Immunol.
volume
129
issue
6
pages
1515 - 1521
Web of Science type
Article
Web of Science id
000304764600011
JCR category
ALLERGY
JCR impact factor
12.047 (2012)
JCR rank
1/23 (2012)
JCR quartile
1 (2012)
ISSN
0091-6749
DOI
10.1016/j.jaci.2012.02.021
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2959880
handle
http://hdl.handle.net/1854/LU-2959880
date created
2012-07-10 11:42:02
date last changed
2012-10-05 13:43:33
@article{2959880,
  abstract     = {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 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 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.},
  author       = {Van Crombruggen, Koen and Holtappels, Gabri{\"e}le and De Ruyck, Natalie and Derycke, Lara and TOMASSEN, PETER and Bachert, Claus},
  issn         = {0091-6749},
  journal      = {JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY},
  keyword      = {RECOGNITION RECEPTOR RAGE,SOLUBLE RECEPTOR,IDIOPATHIC PULMONARY-FIBROSIS,GLYCATION END-PRODUCTS,airway inflammation,Staphylococcus aureus,Receptor for advanced glycation end products,eosinophil cationic protein,LUNG INJURY,NASAL POLYPOSIS,BETA-TOXIN,DIFFERENTIATION,EXPRESSION,SRAGE},
  language     = {eng},
  number       = {6},
  pages        = {1515--1521},
  title        = {RAGE processing in chronic airway conditions: involvement of Staphylococcus aureus and ECP},
  url          = {http://dx.doi.org/10.1016/j.jaci.2012.02.021},
  volume       = {129},
  year         = {2012},
}

Chicago
Van Crombruggen, Koen, Gabriële Holtappels, Natalie De Ruyck, LARA DERYCKE, PETER TOMASSEN, and Claus Bachert. 2012. “RAGE Processing in Chronic Airway Conditions: Involvement of Staphylococcus Aureus and ECP.” Journal of Allergy and Clinical Immunology 129 (6): 1515–1521.
APA
Van Crombruggen, K., Holtappels, G., De Ruyck, N., DERYCKE, L., TOMASSEN, P., & Bachert, C. (2012). RAGE processing in chronic airway conditions: involvement of Staphylococcus aureus and ECP. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 129(6), 1515–1521.
Vancouver
1.
Van Crombruggen K, Holtappels G, De Ruyck N, DERYCKE L, TOMASSEN P, Bachert C. RAGE processing in chronic airway conditions: involvement of Staphylococcus aureus and ECP. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. 2012;129(6):1515–21.
MLA
Van Crombruggen, Koen, Gabriële Holtappels, Natalie De Ruyck, et al. “RAGE Processing in Chronic Airway Conditions: Involvement of Staphylococcus Aureus and ECP.” JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 129.6 (2012): 1515–1521. Print.