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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)
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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.
Keywords
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

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MLA
Van Crombruggen, Koen, et al. “RAGE Processing in Chronic Airway Conditions: Involvement of Staphylococcus Aureus and ECP.” JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, vol. 129, no. 6, 2012, pp. 1515–21, doi:10.1016/j.jaci.2012.02.021.
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. https://doi.org/10.1016/j.jaci.2012.02.021
Chicago author-date
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): 1515–21. https://doi.org/10.1016/j.jaci.2012.02.021.
Chicago author-date (all authors)
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. doi:10.1016/j.jaci.2012.02.021.
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.
IEEE
[1]
K. Van Crombruggen, G. Holtappels, N. De Ruyck, L. Derycke, P. Tomassen, and C. Bachert, “RAGE processing in chronic airway conditions: involvement of Staphylococcus aureus and ECP,” JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, vol. 129, no. 6, pp. 1515–1521, 2012.
@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, Gabriële and De Ruyck, Natalie and Derycke, Lara and Tomassen, Peter and Bachert, Claus}},
  issn         = {{0091-6749}},
  journal      = {{JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY}},
  keywords     = {{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://doi.org/10.1016/j.jaci.2012.02.021}},
  volume       = {{129}},
  year         = {{2012}},
}

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